Ginsenoside composition as well as preparation method and application thereof

Abstract

The invention discloses a ginsenoside composition as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The total ginsenoside composition (TGC), the holographic ginsenoside composition (HGC) and the panaxadiol saponin composition (PDSC) are prepared by scientific compatibility of total saponins extracted from precious traditional Chinese medicinal materials such as ginseng and American ginseng and cheap traditional Chinese medicinal materials such as ginseng stems and leaves, American ginseng stems and leaves and pseudo-ginseng stems and leaves, so that the ginseng traditional Chinese medicinal materials can be saved; the preparation cost of the product can be greatly reduced, the continuous supply of raw materials for industrial production of subsequent TGC, HGC and PDCS products is ensured, and the health-care value and the medicinal value of the product are better realized.

Description

A ginsenoside composition and its preparation method and application Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and specifically relates to a ginsenoside composition, a preparation method and an application thereof. Background Art

[0002] Research into the biological activities and pharmacological effects of Panax ginseng, American ginseng, and Panax notoginseng, as well as the ginsenosides they contain, has long garnered widespread attention from scholars both domestically and internationally. In particular, efforts to elucidate the roles and mechanisms of action of individual ginsenosides, including ginsenotriols (e.g., Rg1, Re, and Rf) and ginsenodiols (e.g., Rb1, Rb2, Rb3, Rc, and Rd), have garnered significant attention. To date, thousands of reviews and research papers have focused on the biological activities of ginseng and ginsenosides, encompassing activities in the central nervous system, cardiovascular system, immune system, endocrine system, and tumors. The main findings can be summarized as follows: 1) Ginseng and ginsenosides exhibit adaptogenic effects (i.e., enhancing the body's ability to respond to various harmful stimuli, thereby mitigating or preventing damage), metabolic regulation, antioxidant, anti-inflammatory, and anti-aging properties. Consistently, as a conceptual understanding, the effects of American ginseng and Panax notoginseng, which also contain ginsenosides as their primary active ingredients, on the central nervous system, cardiovascular system, immune system, energy metabolism, and adaptogens are widely accepted. 2) Panaxatriol saponins, represented by Rg1, and panaxadiol saponins, represented by Rb1, have been extensively studied and reported as antioxidants, anti-inflammatory agents, and mitochondrial metabolism regulators, with protective effects on the nervous and cardiovascular systems. Panaxatriol saponins (Rg1 and Re) and panaxadiol saponins (Rc) can also reduce insulin resistance (i.e., insulin insensitivity). Inhibition of the p38MAPK signaling pathway is considered one of the important mechanisms of action of panaxatriol saponins (Rg1, Re, and Rf) and panaxadiol saponins (Rb1, Rb3, Rc, and Rd). Therefore, panaxatriol saponins and panaxadiol saponins, two structural types, are widely recognized as the primary active ingredients of ginseng, American ginseng, and Panax notoginseng, and are considered to have broad medicinal uses and development prospects. 3) While the biological activities and pharmacological effects of ginsenotriol and ginsenodiol saponins share the aforementioned commonalities, they also exhibit heterogeneous differences. For example, ginsenotriol saponin Rg1 is considered a central nervous system stimulant, while ginsenodiol saponin Rb1 is a central nervous system depressant. Therefore, while these two components give ginseng the ability to regulate the balance of central nervous system excitability and inhibition, they may also antagonize each other in the treatment of related brain diseases, weakening the efficacy and even causing side effects. Consistently, in practical applications, ginseng with a higher Rg1 content and American ginseng with a higher Rb1 content have different therapeutic emphases and cannot replace each other. Furthermore, each has its own applicable disease conditions.4) The biological activities and pharmacological effects of saponins with different structures within the same saponin family share both commonalities and distinct emphases. For example, Rb2 is believed to inhibit TGF-β1 and Smad signaling pathways, activate SIRT1 expression, promote glucose metabolism, reduce fat accumulation, and inhibit epithelial-mesenchymal transition, thereby exerting anti-cancer effects, alleviating myocardial inflammation, reducing oxidative stress, and protecting against myocardial ischemia-reperfusion injury. Rb3 is believed to enhance myocardial function and boost immunity. Rc is believed to have anti-allergic, anti-tumor, analgesic, and sedative effects. In particular, the mechanisms by which ginsenosides produce the same pharmacological effects may differ. For example, different ginsenosides, such as panaxadiols, enhance inhibitory activity in the central nervous system through distinct mechanisms: activating inhibitory GABA receptors (Rc has a strong effect) and glycine receptors (Rb1 has a strong effect), and inhibiting excitatory NMDA receptors (Rg3 has a strong effect). However, panaxatriols, such as Rg1, have no or only weak effects on inhibitory receptor activation.

[0003] In summary, the diverse chemical structures of ginsenosides and the similarities, diversity, heterogeneity, and antagonism in their bioactivities and pharmacological actions reveal the modern scientific implications of the efficacy and medicinal properties of ginseng, American ginseng, and Panax notoginseng as traditional precious Chinese medicines. This has deepened widespread appreciation for the tonic and health-enhancing benefits of these precious Chinese herbs and sparked interest and anticipation in the development of new ginsenoside-based drugs for the prevention and treatment of complex chronic diseases such as brain disorders, cardiovascular diseases, immune disorders, and metabolic syndrome. However, to date, the medicinal value of these traditional precious Chinese herbs is still reflected in the form of total ginsenosides, and with the exception of Dushen Decoction, they are all administered as traditional Chinese medicine compound formulas. Although research and development of new drugs containing individual ginsenosides as active ingredients has received widespread attention, only a few have achieved successful drug development. Clearly, individual ginsenosides cannot carry the full potential of the original medicinal materials, let alone effectively prevent and treat these complex diseases.

[0004] How to leverage the similarities, diversity, and heterogeneity of ginsenosides' biological activities and pharmacological effects to better leverage the tonic and significant medicinal value of these precious Chinese herbs is a crucial and complex scientific challenge. Theoretically, the commonalities, heterogeneity, and opposing effects of the biological activities and pharmacological actions of individual ginsenosides, ginsenodiol saponins, and their analogs make it possible to integrate these active ingredients to create novel medicinal forms encompassing and exceeding the efficacy of ginseng, American ginseng, and Panax notoginseng. However, this integration process is fraught with difficulty and uncertainty.

[0005] Summary of the Invention

[0006] In view of this, the purpose of the present invention is to provide a ginsenoside composition, which can determine the active pharmaceutical ingredients for multiple diseases based on the commonalities, heterogeneity and reverse effects of the biological activities and pharmacological actions exhibited by different individual saponin components of ginsenotriol saponins, ginsenodiol saponins and similar saponins, and can effectively prevent and treat a variety of complex diseases.

[0007] The present invention also aims to provide a method for preparing a ginsenoside composition, which can be used to prevent and treat a variety of different diseases or to exert health care functions based on the complementary characteristics of the different contents of individual saponin components in the total saponins of different medicinal materials of the genus Panax.

[0008] The present invention also aims to provide an application of a ginsenoside composition, which fully and rationally utilizes the unique biological activities and pharmacological effects of each individual ginsenoside and the synergistic effects between ginsenosides, and has great significance and application value in terms of medical or health care applications.

[0009] The present invention provides a ginsenoside composition, which comprises a functional unit 1 and a functional unit 2, wherein the functional unit 1 comprises Rb1 and Rd, and the functional unit 2 comprises Rc and Rb3;

[0010] The mass ratio of the functional unit 1 to the functional unit 2 is 0.66 to 1.92.

[0011] Furthermore, the ginsenoside composition is a ginsenoside composition.

[0012] Furthermore, in the ginsenoside composition, the mass ratio of Rb1 to Rd is 0.79-2.08, the mass ratio of Rb1 to Rc is 0.67-2.17, the mass ratio of Rb1 to Rb3 is 0.82-2.76, and the mass ratio of Rc to Rb3 is 0.79-2.11.

[0013] Furthermore, the mass ratio of Rb1, Rc, Rb3 and Rd is (1.953-2.387):(0.9-1.1):(1.143-1.397):(1.908-2.332), for example, about 2.17:about 1.00:about 1.27:about 2.12.

[0014] Furthermore, the mass ratio of Rb1, Rc, Rb3 and Rd is (1.242-1.518):(0.9-1.1):(0.567-0.693):(1.566-1.914), for example, about 1.38:about 1.00:about 0.63:about 1.74.

[0015] Furthermore, the mass ratio of Rb1, Rc, Rb3 and Rd is (0.9-1.1):(0.9-1.1):(0.423-0.517):(0.576-0.704), for example, about 1.00:about 1.00:about 0.47:about 0.64.

[0016] Furthermore, the mass ratio of Rb1, Rc, Rb3 and Rd is (0.684-0.836):(0.9-1.1):(0.612-0.748):(0.468-0.572), for example, about 0.76: about 1.00: about 0.68: about 0.52.

[0017] Furthermore, the mass ratio of Rb1, Rc, Rb3 and Rd is (0.675-0.825):(0.9-1.1):(0.504-0.616):(0.594-0.726), for example, about 0.75:about 1.00:about 0.56:about 0.66.

[0018] Furthermore, the mass ratio of Rb1, Rc, Rb3 and Rd is (1.251-1.529):(0.9-1.1):(0.981-1.199):(0.819-1.001), for example, about 1.39:about 1.00:about 1.09:about 0.91.

[0019] Furthermore, the mass ratio of Rb1, Rc, Rb3 and Rd is (0.909-1.111):(0.9-1.1):(0.981-1.199):(0.657-0.803), for example, about 1.01:about 1.00:about 1.09:about 0.73.

[0020] In the present invention, the term "about" or "approximately" with respect to a numerical value means ±10% of the numerical value, but explicitly includes the exact numerical value. For example, "about" 1 means from 0.9 to 1.1, but also explicitly includes exactly 1.1.

[0021] Furthermore, the ginsenoside composition further includes Rb2.

[0022] Furthermore, based on the mass of the ginsenoside composition being 100%, the mass percentage of Rb1, Rc, Rb2, Rb3 and Rd is about 85% or more, wherein the mass percentage of Rb2 is 0.1% to 16%.

[0023] Furthermore, the ginsenoside composition is a holographic ginsenoside composition or a total ginsenoside composition.

[0024] Furthermore, the holographic ginsenoside composition or the total ginsenoside composition includes panaxatriol saponins and panaxadiol saponins.

[0025] Furthermore, the ginsenosides include Rg1 and Re.

[0026] Furthermore, the ginsenosides include Rb1, Rb3, Rc and Rd.

[0027] Furthermore, the ratio of the mass of the ginsenosides to the mass of the ginsenosides is 1.88 to 4.41.

[0028] Furthermore, the mass ratio of Re to Rg1 is 2.31 to 4.41.

[0029] Furthermore, the mass ratio of Rb1 to Re is 0.64 to 1.86.

[0030] Furthermore, the mass ratio of Rb1 to Rd is 0.79 to 2.08.

[0031] Furthermore, the mass ratio of Rb1 to Rc is 0.67 to 2.17.

[0032] Furthermore, the mass ratio of Rb1 to Rb3 is 0.82 to 2.76.

[0033] Furthermore, the mass ratio of Rc to Rb3 is 0.79 to 2.11.

[0034] Furthermore, the mass ratio of Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.54~0.66):(1.917~2.343):(1.953~2.387):(0.9~1.1):(1.143~1.397):(1.908~2.332), for example, about 0.60:about 2.13:about 2.17:about 1.00:about 1.27:about 2.12.

[0035] Further, the mass ratio between Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.684~0.836):(1.944~2.376):(1.242~1.518):(0.9~1.1):(0.567~0.693):(1.566~1.914), for example, about 0.76: about 2.16: about 1.38: about 1.00: about 0.63: about 1.74.

[0036] Furthermore, the mass ratio among Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.333-0.407): (0.774-0.946): (0.9-1.1): (0.9-1.1): (0.423-0.517): (0.576-0.704), for example, about 0.37: about 0.86: about 1.00: about 1.00: about 0.47: about 0.64.

[0037] Further, the mass ratio between Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.252~0.308):(0.594~0.726):(0.684~0.836):(0.9~1.1):(0.612~0.748):(0.468~0.572), for example, about 0.28:about 0.66:about 0.76:about 1.00:about 0.68:about 0.52.

[0038] Furthermore, the mass ratio between Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.351~0.429):(0.819~1.001):(0.675~0.825):(0.9~1.1):(0.504~0.616):(0.594~0.726), for example, about 0.39:about 0.91:about 0.75:about 1.00:about 0.56:about 0.66.

[0039] Further, the mass ratio between Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.207~0.253):(0.819~1.001):(1.251~1.529):(0.9~1.1):(0.981~1.199):(0.819~1.001), for example, about 0.23:about 0.91:about 1.39:about 1.00:about 1.09:about 0.91.

[0040] Further, the mass ratio between Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.189~0.231):(0.684~0.836):(0.909~1.111):(0.9~1.1):(0.981~1.199):(0.657~0.803), for example, about 0.21:about 0.76:about 1.01:about 1.00:about 1.09:about 0.73.

[0041] Furthermore, the holographic ginsenoside composition or the total ginsenoside composition further comprises Rb2.

[0042] Furthermore, based on the mass of the holographic ginsenoside composition being 100%, the mass percentage of Rg1, Re, Rb1, Rc, Rb2, Rb3 and Rd is greater than 70%.

[0043] Furthermore, the holographic ginsenoside composition comprises the following components in percentage: 3.22% to 7.71% Rg1, 11.99% to 21.87% Re, 12.62% to 19.82% Rb1, 8.42% to 18.82% Rc, 5.22% to 10.45% Rb2, 6.35% to 17.14% Rb3, and 9.83% to 17.85% Rd.

[0044] Furthermore, based on the mass of the total ginsenoside composition being 100%, the mass percentage of Rg1, Re, Rb1, Rc, Rb2, Rb3 and Rd is greater than 50%.

[0045] Furthermore, the total ginsenoside composition includes the following components in percentage: 2.12% to 5.91% Rg1, 9.05% to 16.77% Re, 9.31% to 19.12% Rb1, 6.42% to 14.33% Rc, 3.58% to 7.96% Rb2, 4.87% to 12.94% Rb3, and 7.28% to 13.60% Rd.

[0046] According to another aspect of the present invention, there is provided a method for preparing the above-mentioned ginsenoside composition, comprising the following steps:

[0047] The total saponins of the original medicinal materials of Panax genus were dissolved and loaded on the reverse phase C 18 In a silica gel chromatography column, elution is first performed with an ethanol aqueous solution having a volume percentage of approximately 43%. When ginsenoside Rb1 is detected, elution is performed with an ethanol aqueous solution having a volume percentage of 50% to 55%. The eluate is collected until ginsenoside Rd is no longer detected in the eluate, and the elution is stopped. The collected eluates are combined to obtain a ginsenoside composition, or fractions of ginsenosides Rb1, Rc, Rb2, Rb3, and Rd are separately collected in combination with online detection and then mixed in the mass ratios mentioned above to obtain a ginsenoside composition;

[0048] Alternatively, the total saponins of the original medicinal materials of Panax genus were dissolved and loaded on a reverse phase C 18 In a silica gel chromatography column, elution is first performed with an ethanol aqueous solution having a volume percentage of approximately 30%. When ginsenoside Rg1 is detected, elution is performed with an ethanol aqueous solution having a volume percentage of 50% to 55%. The eluate is collected until ginsenoside Rd is no longer detected in the eluate, and the elution is stopped. The collected eluates are combined to obtain a holographic ginsenoside composition, or fractions of ginsenosides Rg1, Re, Rb1, Rc, Rb2, Rb3, and Rd are separately collected in combination with online detection and then mixed in the mass ratios mentioned above to obtain a holographic ginsenoside composition;

[0049] Alternatively, the total saponins of Panax genus raw medicinal materials are mixed according to the above-mentioned mass ratio to obtain a total ginsenoside composition.

[0050] Furthermore, the solvent used for the dissolution is an ethanol aqueous solution with a volume percentage of about 30%.

[0051] Furthermore, the mass / volume (mg / mL or g / L) ratio of the total saponins of the Panax raw medicinal material to the approximately 30% ethanol aqueous solution is approximately 1:(8-12).

[0052] Furthermore, before the sample is loaded, the reverse phase C 18 The silica gel chromatography column was equilibrated.

[0053] Furthermore, the inverted C 18 The mass ratio of silica gel to the total saponins of the original medicinal material of Panax genus is (7-10):about 1.

[0054] Furthermore, the Panax genus raw medicinal material is selected from one or more of the following: American ginseng root, American ginseng stem and leaf, ginseng root, ginseng stem and leaf, and Panax notoginseng stem and leaf.

[0055] Furthermore, the total saponins of the Panax genus raw medicinal materials are selected from one or more of the following: total saponins of American ginseng roots, total saponins of American ginseng stems and leaves, total saponins of ginseng roots, total saponins of ginseng stems and leaves, and total saponins of Panax notoginseng stems and leaves.

[0056] Furthermore, in the combination of the total saponins from the roots of American ginseng and the total saponins from the stems and leaves of American ginseng, the mass ratio of the total saponins from the roots of American ginseng to the total saponins from the stems and leaves of American ginseng is about 1:(2-3).

[0057] Furthermore, in the combination of the total saponins from ginseng roots, the total saponins from American ginseng roots, the total saponins from ginseng stems and leaves, and the total saponins from American ginseng stems and leaves, the mass ratio of the total saponins from ginseng roots, the total saponins from American ginseng roots, the total saponins from ginseng stems and leaves, and the total saponins from American ginseng stems and leaves is about 1:about 1:about 1:about 3.

[0058] Furthermore, in the combination of the total saponins from ginseng roots, the total saponins from ginseng stems and leaves, and the total saponins from Panax notoginseng stems and leaves, the mass ratio of the total saponins from ginseng roots, the total saponins from ginseng stems and leaves, and the total saponins from Panax notoginseng stems and leaves is (1-2): about 1: about (1-2).

[0059] Furthermore, in the combination of the total saponins from American ginseng roots, the total saponins from American ginseng stems and leaves, and the total saponins from Panax notoginseng stems and leaves, the mass ratio of the total saponins from American ginseng roots, the total saponins from American ginseng stems and leaves, and the total saponins from Panax notoginseng stems and leaves is about 1:about 1:(1-2).

[0060] Furthermore, the total saponins of the Panax genus raw medicinal material are extracted from the Panax genus raw medicinal material or are commercial products.

[0061] Furthermore, the total saponins of Panax genus raw medicinal materials are obtained by mixing the respective Panax genus raw medicinal materials and then preparing them using the following method, or by first preparing the total saponins of the respective Panax genus raw medicinal materials separately using the following method and then mixing them:

[0062] (1) extracting (e.g., percolation extraction) three times using a solvent (e.g., water or an aqueous ethanol solution with a volume percentage of 5% to 95%, such as 50% to 70%), and removing the solvent to obtain a first extract;

[0063] (2) extracting the first extract three times with n-butanol, combining the extracts to obtain a second extract;

[0064] (3) separating the second extract by macroporous resin column chromatography, eluting with about 30% ethanol aqueous solution and about 70% ethanol aqueous solution, collecting the about 70% ethanol eluate, and removing the solvent to obtain a third extract; and

[0065] (4) Decolorizing the third extract with a macroporous ion exchange resin, eluting with deionized water, collecting the eluate and concentrating to dryness.

[0066] Furthermore, the macroporous resin is Diaion HP 20 macroporous resin.

[0067] Furthermore, the mass ratio of the macroporous resin to the second extract is (8-10):about 1.

[0068] Furthermore, in the macroporous resin column chromatography, the usage of about 30% ethanol aqueous solution and about 70% ethanol aqueous solution is 3 to 5 column volumes, respectively.

[0069] Furthermore, the macroporous ion exchange resin is D201 macroporous anion exchange resin.

[0070] Furthermore, the mass ratio of the macroporous ion exchange resin to the third extract is (8-10):about 1.

[0071] Furthermore, the amount of deionized water used for elution is 4 to 6 column volumes.

[0072] According to another aspect of the present invention, there is provided a use of the ginsenoside composition or the ginsenoside composition prepared by the above preparation method in preparing a drug for preventing and / or treating a disease.

[0073] Furthermore, the ginsenoside composition includes a total ginsenoside composition (ie, a first ginsenoside composition), a holographic ginsenoside composition (ie, a second ginsenoside composition), and / or a ginsenodiol saponin composition (ie, a third ginsenoside composition).

[0074] Furthermore, the disease includes at least one of the following: nervous system disorders, autoimmune diseases, stress diseases, aging and related diseases, fundus diseases, skin diseases and mitochondrial diseases.

[0075] Furthermore, the neurological disorder includes at least one of the following: mental illness, sleep disorder, neurodevelopmental delay and / or developmental disorder, nerve damage and dysfunction disease, neurodegenerative disease, addictive disease and peripheral neuropathy disease.

[0076] Furthermore, the mental illness includes at least one of the following: schizophrenia, depression, bipolar disorder, anxiety disorder and mania.

[0077] Furthermore, the sleep disorder includes at least one of the following: difficulty falling asleep, difficulty maintaining sleep, early awakening, decreased sleep quality, frequent dreams, and reduced total sleep time; at the same time, it is accompanied by daytime functional disorders, such as daytime sleepiness, fatigue, inattention, memory loss, accompanied by nervousness, compulsion, and depression.

[0078] Furthermore, the neurodevelopmental delay and / or developmental disorder comprises at least one of the following: hyperactivity, inattention, learning disabilities, attention deficit hyperactivity disorder / ADHD, autism, language disorders, sleep disorders, Tourette syndrome / tics and Tourette syndrome.

[0079] Furthermore, the neurological injury and dysfunction diseases include at least one of the following: delirium, perioperative neurocognitive disorder, migraine, epilepsy, neuropsychiatric dysfunction and akinesia sequelae in the acute and chronic stages of stroke, basal ganglia neural circuit dysfunction, restless legs syndrome and hypertonia.

[0080] Furthermore, the basal ganglia neural circuit dysfunction disorder includes at least one of the following: chorea, athetosis, and dystonia syndrome.

[0081] Furthermore, the neurodegenerative disease includes at least one of the following: Parkinson's syndrome, Alzheimer's disease, vascular dementia, mixed dementia, secondary dementia, cerebral atrophy, chorea, multiple sclerosis and amyotrophic lateral sclerosis.

[0082] Furthermore, the Parkinson's syndrome includes at least one of the following: multiple system degeneration-Parkinson's plus syndrome, primary Parkinson's syndrome, atypical Parkinson's syndrome, juvenile Parkinson's syndrome, secondary Parkinson's syndrome caused by infection or ischemia, hereditary degenerative Parkinson's syndrome and extrapyramidal reaction caused by drug treatment.

[0083] Furthermore, the multiple system degeneration-parkinsonism plus syndrome includes at least one of the following: multiple system atrophy, progressive supranuclear palsy, dementia with Lewy bodies, brain iron accumulation neurodegeneration type I, diffuse Lewy body disease, Lewy body variant of Alzheimer's disease, corticobasal degeneration and frontotemporal lobar degeneration.

[0084] Furthermore, the addictive disease includes at least one of the following: alcohol and drug addiction, adolescent internet and game addiction, and pathological gambling.

[0085] Furthermore, the peripheral neuropathy disease includes at least one of the following: neuralgia, facial neuritis, hemifacial spasm, multiple peripheral neuropathy, neurodermatitis, Guillain-Barré syndrome, and neuralgia and movement disorders caused by viral infection.

[0086] Furthermore, the autoimmune disease includes at least one of the following: lupus erythematosus, autoimmune glomerulonephritis, rheumatoid arthritis, dermatomyositis, scleroderma, allergic rhinitis, allergic asthma, urticaria, allergic dermatitis, allergic conjunctivitis, demyelinating disease, connective tissue disease, neuromuscular disease, digestive system disease, endocrine disease and urinary system disease.

[0087] Furthermore, the connective tissue disease includes at least one of the following: systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis and scleroderma.

[0088] Furthermore, the neuromuscular disease includes at least one of the following: multiple sclerosis, myasthenia gravis and demyelinating disease.

[0089] Furthermore, the digestive system disease includes at least one of the following: chronic nonspecific ulcerative colitis, chronic active hepatitis, pernicious anemia, and atrophic gastritis.

[0090] Furthermore, the endocrine disease includes at least one of the following: primary adrenal cortical atrophy and chronic thyroiditis.

[0091] Furthermore, the urinary system disease includes autoimmune glomerulonephritis and / or pulmonary-renal hemorrhagic syndrome.

[0092] Furthermore, the stress-induced diseases include sub-health conditions and / or stress-induced traumatic sequelae caused by chronic stress.

[0093] Furthermore, the sub-health state includes at least one of the following: insomnia, frequent dreams and daytime dysfunction and their related daytime sleepiness, fatigue, inattention, memory loss, reduced work efficiency and creativity, or accompanied by nervousness, anxiety, compulsion, and depression.

[0094] Furthermore, the stress-traumatic sequelae include at least one of the following: acute stress disorder, maladjustment and post-traumatic stress disorder.

[0095] Furthermore, the aging and related diseases include at least one of the following: premature aging, heart aging, memory loss in the elderly, senile hypertension, senile sleep disorders, senile constipation, senile / degenerative frequent urination and urgency, and chronic inflammation in the elderly.

[0096] Furthermore, the fundus disease includes at least one of the following: retinal vasculitis, retinal vascular occlusion, diabetic retinopathy, optic neuropathy, macular edema and age-related macular degeneration;

[0097] Furthermore, the skin disease includes at least one of the following: pellagra, drug-induced skin disease, and disease-induced skin disease;

[0098] Preferably, the mitochondrial disease includes mitochondrial myopathy and mitochondrial encephalomyopathy.

[0099] Furthermore, the dosage form of the drug includes liquid preparations and / or solid preparations.

[0100] Furthermore, the liquid preparation includes an oral solution and / or an injection solution.

[0101] Furthermore, the solid preparation is selected from the group consisting of tablets, capsules, granules, pills, enteric-coated preparations, controlled-release preparations and nanoformulations.

[0102] Furthermore, the use includes the use of the ginsenoside composition or the holographic ginsenoside composition as the sole active ingredient and / or the use of the ginsenoside composition or the holographic ginsenoside composition in combination with other drugs to prepare a compound preparation to enhance the synergy and reduce the toxicity of existing drugs.

[0103] Furthermore, the other drugs include at least one of the following drugs: levodopa drugs and dopamine type 2 receptor agonists for treating Parkinson's disease, dopamine receptor inhibitors for treating schizophrenia and anxiety disorders, sodium / calcium channel inhibitors for treating epilepsy and nerve damage and for treating neuropsychiatric and behavioral disorders characterized by glutamate hyperexcitability or GABA inhibition deficiency, mycophenolate mofetil for treating autoimmune diseases and organ transplant rejection, anti-tumor chemotherapy drugs or targeted drugs.

[0104] Furthermore, the levodopa-like drugs include at least one of the following: Madopar, Sinemet and Darlingfor.

[0105] Furthermore, the dopamine type 2 receptor agonist comprises at least one of the following: sefrol, ropinirole and cabergoline.

[0106] Furthermore, the dopamine receptor inhibitor includes at least one of the following: haloperidol, olanzapine, clozapine and risperidone.

[0107] Furthermore, the sodium and calcium ion channel inhibitors include at least one of the following: lamotrigine, gabapentin, or pregabalin.

[0108] Furthermore, the ginsenoside composition and lamotrigine are used in combination or the composite medicine prepared from the two to exert synergistic and toxicity-reducing effects, and are used to treat epilepsy, bipolar disorder, and acute cerebral ischemic injury.

[0109] Furthermore, the acute cerebral ischemic injury includes at least one of the following: acute cerebral stroke and neonatal cerebral ischemia.

[0110] Furthermore, when the ginsenoside composition and the gabapentin or pregabalin are used in combination or the composite drug prepared by the two exerts a synergistic and toxicity-reducing effect, it is used to treat developmental delay or developmental disorders, alcohol and drug addiction, adolescent internet and game addiction and pathological gambling, neuropathic pain, anxiety and sleep disorders.

[0111] Furthermore, the chemotherapy drug or target drug includes at least one of the following: paclitaxel and a tyrosine kinase inhibitor.

[0112] According to another aspect of the present invention, there is provided a use of the ginsenoside composition or the ginsenoside composition prepared by the preparation method according to any one of claims 4 to 6 in preparing a health-care product having health-care functions.

[0113] Furthermore, the health care function includes at least one of the following: delaying aging, improving the health level and quality of life of the elderly, improving sub-health status and alleviating side effects of neurological system caused by drug treatment.

[0114] Furthermore, the neurological side effects caused by the drug treatment include neurological side effects caused by neuropsychiatric drugs or anti-tumor drugs.

[0115] Furthermore, the neuropsychiatric drugs include at least one of the following: dopamine receptor inhibitors and agonists, levodopa drugs, serotonin drugs, sodium and calcium ion channel inhibitors, glutamate receptor inhibitors and other neurotransmitter receptor inhibitors.

[0116] Furthermore, the anti-tumor drug includes at least one of the following: a chemotherapy drug, a molecular targeted drug, and an immunotherapy drug.

[0117] Furthermore, the delaying of aging includes at least one of the following: inhibiting or preventing premature aging, improving memory loss in the elderly, improving sleep in the elderly, increasing appetite, alleviating chronic inflammatory conditions in the elderly, improving the mobility of the elderly and prolonging healthy life expectancy.

[0118] Furthermore, the sub-health state includes at least one of the following states: insomnia, frequent dreams, sleep disorders, tension, anxiety, depression, memory loss, physical and mental fatigue and reduced work efficiency.

[0119] Furthermore, the health care product includes a liquid health care product and / or a solid health care product.

[0120] Furthermore, the liquid health care product includes an oral liquid.

[0121] Furthermore, the solid health care product comprises at least one of the following: tablets, capsules, granules and pills.

[0122] According to another aspect of the present invention, a preparation comprising the above ginsenoside composition or the ginsenoside composition prepared by the above preparation method is provided, wherein the preparation comprises at least one of the following ingredients: a nutrient ingredient and an active ingredient.

[0123] Furthermore, the nutrient component includes at least one of the following: protein, polypeptide and glutathione precursor amino acid, NAD + Precursors and nucleic acids.

[0124] Furthermore, the active ingredient includes at least one of the following: a Chinese herbal medicine extract that is both medicinal and edible, coenzyme Q10, vitamins, and energy metabolism intermediates.

[0125] Furthermore, the dosage form of the preparation is an oral preparation.

[0126] Furthermore, the oral preparation includes a solid preparation and / or a liquid preparation.

[0127] Furthermore, the solid preparation is selected from the group consisting of capsules, ordinary tablets, dispersible tablets, enteric-coated tablets and granules.

[0128] The ginsenoside composition provided by the present invention comprises a functional unit 1 formed by Rb1 and Rd and a functional unit 2 formed by Rc and Rb3; the mass ratio of the functional unit 1 formed by Rb1 and Rd to the functional unit 2 formed by Rc and Rb3 is 0.66-1.92. The present invention clarifies the influence of the central excitatory effect of ginsenosides of ginsenosides on the central inhibitory effect of ginsenosides of ginsenosides through the experiment of decomposing the active ingredients of total saponins of Panax genus Chinese medicinal materials, and further analyzes and verifies that the content of ginsenoside Rb2 does not affect the efficacy of the ginsenoside composition, and determines that ginsenosides Rb1, Rb3, Rc and Rd are the main active ingredients of the efficacy of the ginsenoside composition, and these four active ingredients constitute the two functional units of "Rb1+Rd" and "Rc+Rb3". These two functional units respectively play the wonderful role of direct implementers and coordinators of their therapeutic effects on different diseases or different symptoms of the same disease. The subtle synergistic effect of the two (neither of them can be missing) not only eliminates their respective efficacy defects, but also greatly improves the efficacy, safety and stability of the product, and increases the range of effective doses. The present invention uses scientific compatibility of ginsenosides to enable Rb1, Rb3, Rc and Rd to each exert unique biological activities and pharmacological effects, while at the same time synergizing with each other to effectively prevent and treat major diseases including neurodegenerative diseases.

[0129] Furthermore, according to the differences in the types and contents of the active ingredients in the present invention, the ginsenoside composition is specifically divided into a holographic ginsenoside composition (HGC) (also referred to herein as the "second ginsenoside composition"), a panaxadiol saponins composition (PDSC) (also referred to herein as the "third ginsenoside composition"), and a total ginsenoside composition (TGC) (also referred to herein as the "first ginsenoside composition"). The three compositions strictly limit the ratios between individual ginsenosides, thereby further endowing the compositions with the following technical features: (1) integrating the biological and pharmacological activities of different ginsenosides in Panax genus Chinese herbal medicines and their total saponins, thus having a wide range of health care and disease prevention values; (2) avoiding the central excitatory effect of ginsenotriol saponins weakening the central inhibitory effect of ginsenodiol saponins; (3) avoiding the central excitatory effect of ginsenotriol saponins that may produce effects inconsistent with the product function; (4) the seven preferred ratios of ginsenosides provide multiple solutions for the flexible use of Panax genus Chinese herbal medicine raw materials to prepare the target composition products, which can alleviate the shortage of Panax genus Chinese herbal medicine resources and improve their utilization efficiency. TGC and / or HGC are characterized by strong functionality, stability, reliability and high safety. PDSC further eliminates the direct side effects of triol saponins' central excitability and their weakening of the pharmacological effects of diol saponins in any use scenario. This makes PDSC more clinically suitable than HGC for the prevention and treatment of neurological diseases characterized by hyperexcitability of glutamate and insufficient inhibitory activity of γ-aminobutyric acid. Furthermore, the seven preferred ratios of the TGC and HGC quality standards and the seven preferred ratios of the PDSC quality standards provide multiple options for the flexible use of available Panax genus medicinal materials to prepare target products, alleviating the shortage of Panax genus medicinal materials and improving their utilization efficiency.

[0130] Furthermore, the present invention specifically stipulates that the ginsenoside composition also includes Rb2. As an ingredient that is irrelevant or not closely related to pharmaceutical and health care effects, Rb2 is allowed to exist in its natural state in holographic ginsenoside composition (HGC), ginsenoside diol composition (PDSC) and total ginsenoside composition (TGC) products.

[0131] The present invention provides a preparation method of the ginsenoside composition, wherein the present invention uses Chinese medicinal materials of the genus Panax as raw materials, uses alcohol aqueous solution as extraction solvent, extracts with n-butanol, separates with macroporous resin and decolorizes with macroporous ion exchange resin to obtain the total ginsenoside composition or mixes the total saponins of Chinese medicinal materials of the genus Panax, and then performs reverse phase C18 The preparation method of the present invention has easy-to-obtain raw materials and good reproducibility, laying a foundation for the development of clinical drugs and the preparation of health care products. BRIEF DESCRIPTION OF THE DRAWINGS

[0132] Figure 1. Effects of ROT in Example 10-2 on p-p65 levels in mouse microvascular endothelial cells (bEnd.3), primary mouse astrocytes (ASC) and microglia (MCG), and dopamine neuron PC12 cells.

[0133] Figure 2. The pathological progression of neurovascular unit and α-synuclein during the development and progression of the ROT-induced PD rat model in Example 10-6, and the role of PDSC1.

[0134] Figure 3. Effects of ROT and PDSC1 on the striatum and substantia nigra pars compacta (SNc) and their GFAP, NF-B and iNOS in Example 10-6.

[0135] Figure 4 shows the protective effect of PDSC1 on vascular damage and surrounding astrocytes in the striatum and substantia nigra of PD animals in Example 10-6, and the efficacy of PDSC1 maintained by combining with L-DOPA.

[0136] Figure 5. Protective effect of PDSC1 in Example 10-6 on microvascular and blood-brain barrier damage in the striatum, substantia nigra pars compacta and ventral part of the brain of PD animals.

[0137] Figure 6 shows the reduction of PV-positive neurons in the striatum of PD rats induced by ROT and the protective effect of PDSC1 in Example 11.

[0138] Figure 7. Neuroprotective effect of PDSC1 against global cerebral ischemia in Mongolian gerbils in Example 16. A: Shows typical changes in the CA1 region of the hippocampus in each experimental group 7 days after ischemia; B: Shows the number of surviving or degenerating neurons within the middle 250 μm of the CA1 region in each group (mean ± SEM). ++p < 0.001 vs. sham control group; *p < 0.05, **p < 0.01 vs. model control group; #p < 0.05 vs. MK-801 group.

[0139] Figure 8 shows the neurological damage in the hippocampus over time after ischemia and the neuroprotective effect of PDSC1 in Example 16. The mean number (SEM) of surviving neurons in the 250 μm long CA1 middle region at each time point is shown, **p<0.01 vs. model control group.

[0140] Figure 9. Neuroprotective effect of PDSC1 against global cerebral ischemia in Mongolian gerbils in Example 16. The figure shows the mean number of surviving or degenerating neurons in the 250 μm-long central CA1 region (mean ± SEM). ++p < 0.001 vs. sham control group; *p < 0.05 vs. model control group; #p < 0.05 vs. MK-801 group.

[0141] Figure 10. Neurological deficits after focal ischemia induced by angiotensin ET-1 and the protective effect of PDSC1 in rats in Example 16. The figure shows the mean behavioral scores (mean ± SEM) of each experimental group; *p < 0.05, **p < 0.001 vs. the model group.

[0142] Figure 11. Neuroprotective effect of PDSC1 against ET-1-induced focal ischemia in rats in Example 16. A: Typical histological changes in the cortex and hippocampus; B: Lesion volumes in the cortex and striatum; ++p < 0.01 vs. sham group; *p < 0.05, **p < 0.01 vs. model group.

[0143] Figure 12. The combination of PDSC1 and lamotrigine in Example 17-1 produces excellent anti-epileptic efficacy in the acute epilepsy model induced by isoniazid and thiosemicarbazide.

[0144] Figure 13. PDSC1 alone and in combination with LTG in Example 17-2 has a good therapeutic effect on pilocarpine-induced refractory chronic epilepsy in rats.

[0145] Figure 14. The combination of PDSC1 and LTG in Example 17-4 can counteract the side effects of LTG-induced dermatitis in mice.

[0146] FIG15 shows the development of butterfly-shaped erythema on the cheeks of pristane-induced systemic lupus erythematosus (SLE) model mice in Example 18.

[0147] Figure 16 is a comparison of butterfly-shaped erythema on the cheeks of mice in each group treated with drug for 60 days in Example 18. DETAILED DESCRIPTION

[0148] The present invention provides a ginsenoside composition, which includes a functional unit 1 and a functional unit 2, wherein the functional unit 1 includes Rb1 and Rd, and the functional unit 2 includes Rc and Rb3; the mass ratio of the functional unit 1 to the functional unit 2 is 0.66-1.92.

[0149] In the present invention, according to the proportion of active ingredients and the difference in the types of active ingredients, the ginsenoside composition preferably includes a ginsenoside composition (PDSC), a holographic ginsenoside composition (HGC), and a total ginsenoside composition (TGC). The experimental screening of the present invention determined that the four ginsenosides Rb1, Rb3, Rc and Rd are the main active ingredients of the ginsenoside composition, and these four active ingredients constitute the two functional units of "Rb1+Rd" and "Rc+Rb3". These two functional units play the wonderful role of direct implementers and coordinators of their therapeutic effects on different diseases or different symptoms of the same disease, and the subtle synergistic effect of the two (neither of them can be missing) not only eliminates their respective efficacy defects, but also greatly improves the efficacy, stability and safety of the product, and increases the range of effective doses. In particular, the PDSC product further completely eliminates the side effect of the central excitatory effect of ginsenosides weakening the central inhibitory effect of ginsenosides in any use scenario, which gives the PDSC product a clinical positioning feature that is more suitable for preventing and treating neurological diseases characterized by glutamate excitability and γ-aminobutyric acid inhibition than the holographic ginsenoside composition (HGC) product. The experimental results of the embodiment of alleviating the motor symptoms of Parkinson's syndrome show that in the composition, the functional unit 1 formed by Rb1 and Rd is the direct implementer of the drug effect, but its effective dosage range is narrow, and the dose-effect relationship shows a jump-type bidirectional change, while the functional unit 2 formed by Rc and Rb3 is the coordinator. The functional unit 2 formed by Rc and Rb3 synergizes with the functional unit 1 formed by Rb1 and Rd to exert positive drug effects, while at the same time restraining the side effects of the functional unit 1 formed by Rb1 and Rd, thereby making the overall drug effect significant, stable and reliable. On the contrary, the experimental results of the embodiment of the efficacy against the occurrence and development of Parkinson's disease prove that the functional unit 2 is the direct implementer of the efficacy, but its effective dosage range is narrow and even has a point-like distribution, while the functional unit 1 may aggravate the occurrence and development of PD or show a weak protective efficacy depending on its dosage, but can cooperate with the functional unit 2 to produce a stronger efficacy and greatly expand the effective dosage range.

[0150] In the present invention, in the ginsenoside composition, the mass ratio of Rb1 to Rd is 0.79-2.08, the mass ratio of Rb1 to Rc is 0.67-2.17, the mass ratio of Rb1 to Rb3 is 0.82-2.76, and the mass ratio of Rc to Rb3 is 0.79-2.11; the mass ratio of (Rb1+Rd) / (Rc+Rb3) is preferably 0.66-1.92. Furthermore, the mass ratios of Rb1, Rc, Rb3, and Rd are (1.953-2.387):(0.9-1.1):(1.143-1.397):(1.908-2.332), for example, about 2.17:about 1.00:about 1.27:about 2.12. Furthermore, the mass ratio of Rb1, Rc, Rb3, and Rd is (1.242-1.518): (0.9-1.1): (0.567-0.693): (1.566-1.914), for example, about 1.38: about 1.00: about 0.63: about 1.74. Furthermore, the mass ratio of Rb1, Rc, Rb3, and Rd is (0.9-1.1): (0.9-1.1): (0.423-0.517): (0.576-0.704), for example, about 1.00: about 1.00: about 0.47: about 0.64. Furthermore, the mass ratio of Rb1, Rc, Rb3, and Rd is (0.684-0.836): (0.9-1.1): (0.612-0.748): (0.468-0.572), for example, about 0.76: about 1.00: about 0.68: about 0.52. Furthermore, the mass ratio of Rb1, Rc, Rb3, and Rd is (0.675-0.825): (0.9-1.1): (0.504-0.616): (0.594-0.726), for example, about 0.75: about 1.00: about 0.56: about 0.66. Furthermore, the mass ratio of Rb1, Rc, Rb3, and Rd is (1.251-1.529): (0.9-1.1): (0.981-1.199): (0.819-1.001), for example, about 1.39: about 1.00: about 1.09: about 0.91. Further, the mass ratio of Rb1, Rc, Rb3, and Rd is (0.909-1.111): (0.9-1.1): (0.981-1.199): (0.657-0.803), for example, about 1.01: about 1.00: about 1.09: about 0.73. As used herein, "about" refers to a value within a range of ±10% of a particular value. For example, "about 1" includes ±10% of 1, or from 0.9 to 1.0, inclusive. The present invention uses the above 6 ratios as the preferred quality standard for the ginsenoside composition and the basis for the mixing ratio of the Chinese medicinal materials or total saponin raw materials used in its preparation.Moreover, the seven preferred Rb1 / Rc / Rb3 / Rd ratios provide many solutions for flexibly utilizing the mixed configuration of Panax genus Chinese herbal medicine raw materials to prepare target composition products, which can alleviate the shortage of Panax genus Chinese herbal medicine resources and improve their utilization efficiency.

[0151] In the present invention, the ginsenoside composition preferably further includes Rb2. Rb2 is an ingredient that is irrelevant or not very relevant to the medical and health care effects, and is allowed to exist in the ginsenoside composition product in its natural state. The ginsenoside composition is 100%, and the total mass percentage of ginsenosides in the ginsenoside composition is preferably about 85% or more, more preferably 90% or more, specifically including the following percentages: 19.93% to 28.14% Rb1, 12.95% to 26.30% Rc, 7.32% to 15.32% Rb2, 10.61% to 23.88% Rb3, and 13.73% to 29.47% Rd. In the present invention, the holographic ginsenoside composition or the total ginsenoside composition contains the same active ingredients, the only difference being the different proportions of the active ingredients, preferably including panaxatriol saponins and ginsenosides. The ginsenosides are preferably Rg1 and Re; the ginsenosides are preferably Rb1, Rb3, Rc and Rd. The holographic ginsenoside composition meets the 8-ratio standard. Preferably, the ratio of the total mass of ginsenosides to the total mass of ginsenosides is 1.88-4.41, the mass ratio of Re to Rg1 is 2.31-4.41, the mass ratio of Rb1 to Re is 0.64-1.86, the mass ratio of Rb1 to Rd is 0.79-2.08, the mass ratio of Rb1 to Rc is 0.67-2.17, and the mass ratio of Rb1 to Rb3 is 0. 82~2.76, the mass ratio of Rc and Rb3 is 0.79~2.11; further, the mass ratio of Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.54~0.66):(1.917~2.343):(1.953~2.387):(0.9~1.1):(1.143~1.397):(1.908~2.332), for example, about 0.60:about 2.13:about 2.17 : about 1.00: about 1.27: about 2.12; further, the mass ratios of Rg1, Re, Rb1, Rc, Rb3 and Rd are (0.684-0.836): (1.944-2.376): (1.242-1.518): (0.9-1.1): (0.567-0.693): (1.566-1.914), for example, about 0.76: about 2.16: about 1.38: about 1.00 : about 0.63: about 1.74; further, the mass ratios of Rg1, Re, Rb1, Rc, Rb3 and Rd are (0.333-0.407): (0.774-0.946): (0.9-1.1): (0.9-1.1): (0.423-0.517): (0.576-0.704), for example, about 0.37: about 0.86: about 1.00: about 1.00: about 0.47: about 0.64; further, the mass ratios of Rg1, Re, Rb1, Rc, Rb3, and Rd are (0.252-0.308): (0.594-0.726): (0.684-0.836): (0.9-1.1): (0.612-0.748): (0.468-0.572), for example, about 0.28: about 0.66: about 0.76: about 1.00: about 0.68: about 0. 52; further, the mass ratios of Rg1, Re, Rb1, Rc, Rb3 and Rd are (0.351-0.429): (0.819-1.001): (0.675-0.825): (0.9-1.1): (0.504-0.616): (0.594-0.726), for example, about 0.39: about 0.91: about 0.75: about 1.00: about 0.56: about 0.6 6; Further, the mass ratio of Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.207-0.253): (0.819-1.001): (1.251-1.529): (0.9-1.1): (0.981-1.199): (0.819-1.001), for example, about 0.23: about 0.91: about 1.39: about 1.00: about 1.09: about 0.91 ; Further, the mass ratios of Rg1, Re, Rb1, Rc, Rb3 and Rd are (0.189-0.231): (0.684-0.836): (0.909-1.111): (0.9-1.1): (0.981-1.199): (0.657-0.803), for example, about 0.21: about 0.76: about 1.01: about 1.00: about 1.09: about 0.73. The present invention uses the above seven Rg1 / Re / Rb1 / Rc / Rb3 / Rd ratios to be independent of each other, that is, each of the preferred ratios represents a composition product composed of Rg1, Re, Rb1, Rc, Rb3 and Rd according to their specific ratios, which constrains the ratio of ginsenotriol saponins to ginsenodiol saponins and the ratio between each individual ginsenoside. Therefore, the following technical features are further endowed to the composite product: (1) the biological activities and pharmacological activities of different ginsenosides in the Panax genus Chinese herbal medicine and its total saponins are integrated, thus having a wide range of health care and disease prevention value; (2) the central excitatory effect of ginsenotriol saponins is avoided from weakening the central inhibitory effect of ginsenodiol saponins; (3) the central excitatory effect of ginsenotriol saponins is avoided from producing effects that are inconsistent with the product function; (4) these seven preferred ratios provide multiple solutions for the flexible use of the mixed preparation of Panax genus Chinese herbal medicine raw materials to prepare the target composite product, which can alleviate the shortage of Panax genus Chinese herbal medicine resources and improve their utilization efficiency.

[0152] In the present invention, the structural formulas of Rg1 and Re are shown in Structural Formula I:

[0153] Wherein, Rg1 represents ginsenoside Rg1 (R=H), and Re represents ginsenoside Re (R=6-deoxy-1-methylpyranosyl).

[0154] The structural formulas of Rb1, Rc, Rb2, Rb3 and Rd are shown in Structural Formula II:

[0155] Among them, Rb1 represents ginsenoside Rb1 (R = β-D-pyranose glucopyranosyl), Rc represents ginsenoside Rc (R = α-L-arabinofuranosyl), Rb2 represents ginsenoside Rb2 (R = α-L-arabinopyranosyl), Rb3 represents ginsenoside Rb3 (R = β-D-pyranose glucopyranosyl), and Rd represents ginsenoside Rd (R = H).

[0156] In the present invention, the holographic ginsenoside composition or total ginsenoside composition preferably further comprises Rb2. As an ingredient irrelevant or insignificant to the aforementioned medicinal and health care effects, Rb2 is permitted to exist in the holographic ginsenoside composition (HGC) and total ginsenoside composition (TGC) products at a natural level.

[0157] In the present invention, the holographic ginsenoside composition is 100%, and the total mass percentage of Rg1, Re, Rb1, Rc, Rb2, Rb3 and Rd is more than 70%, more preferably more than 80%, and specifically includes the following components in percentage: 3.22% to 7.71% Rg1, 11.99% to 21.87% Re, 12.62% to 19.82% Rb1, 8.42% to 18.82% Rc, 5.22% to 10.45% Rb2, 6.35% to 17.14% Rb3, and 9.83% to 17.85% Rd.

[0158] In the present invention, the total ginsenoside composition is 100%, and the total mass percentage of Rg1, Re, Rb1, Rc, Rb2, Rb3 and Rd is more than 50%, more preferably more than 60%, and specifically includes the following components in percentage: 2.12% to 5.91% Rg1, 9.05% to 16.77% Re, 9.31% to 19.12% Rb1, 6.42% to 14.33% Rc, 3.58% to 7.96% Rb2, 4.87% to 12.94% Rb3, and 7.28% to 13.60% Rd.

[0159] The present invention provides a method for preparing the ginsenoside composition, specifically a method for preparing a ginsenoside composition, a holographic ginsenoside composition, or a total ginsenoside composition, comprising the following steps:

[0160] The total saponins of the original medicinal materials of Panax genus were dissolved and loaded on the reverse phase C 18 In a silica gel chromatography column, elution is performed with a 43% by volume ethanol aqueous solution. When ginsenoside Rb1 is detected, elution is performed with a 50-55% by volume ethanol aqueous solution and the eluate is collected until ginsenoside Rd is no longer detected in the eluate. The combined eluate is concentrated and dried to obtain a ginsenoside composition.

[0161] Alternatively, the total saponins of the original medicinal materials of Panax genus were dissolved and loaded onto a reverse phase C 18 In a silica gel chromatography column, elution is performed with a 30% by volume ethanol aqueous solution. When ginsenoside Rg1 is detected, elution is performed with a 50-55% by volume ethanol aqueous solution and the eluate is collected until ginsenoside Rd is no longer detected in the eluate. The combined eluate is concentrated and dried to obtain a holographic ginsenoside composition.

[0162] Alternatively, the total saponins of Panax genus raw medicinal materials are mixed according to the above-mentioned mass ratio to obtain a total ginsenoside composition.

[0163] In the present invention, based on the difference in the content of individual ginsenosides in different parts of various Chinese medicinal materials of the genus Panax, a ginsenoside composition is prepared by mixing and preparing according to specific uses. The present invention prepares a ginsenoside composition using American ginseng roots, American ginseng stems and leaves, ginseng roots, ginseng stems and leaves, Panax notoginseng stems and leaves, or their corresponding total saponins as raw materials. The total saponins of the original medicinal materials of the genus Panax preferably include the following combinations: a combination of total saponins of American ginseng roots and total saponins of American ginseng stems and leaves, a combination of total saponins of ginseng roots, total saponins of American ginseng roots, total saponins of ginseng stems and leaves, and total saponins of American ginseng stems and leaves, a combination of total saponins of ginseng roots, total saponins of ginseng stems and leaves, and total saponins of Panax notoginseng stems and leaves, and a combination of total saponins of American ginseng roots, total saponins of American ginseng stems and leaves, and total saponins of Panax notoginseng stems and leaves. Among them, in the combination of total saponins of American ginseng roots and total saponins of American ginseng stems and leaves, the mass ratio of total saponins of American ginseng roots and total saponins of American ginseng stems and leaves is preferably about 1:(2-3). In the combination of total saponins from ginseng roots, total saponins from American ginseng roots, total saponins from ginseng stems and leaves, and total saponins from American ginseng stems and leaves, the mass ratio of total saponins from ginseng roots, total saponins from American ginseng roots, total saponins from ginseng stems and leaves, and total saponins from American ginseng stems and leaves is preferably about 1:about 1:about 1:about 3. In the combination of total saponins from ginseng roots, total saponins from ginseng stems and leaves, and total saponins from Panax notoginseng stems and leaves, the mass ratio of total saponins from ginseng roots, total saponins from ginseng stems and leaves, and total saponins from Panax notoginseng stems and leaves is preferably (1-2):about 1:(1-2), and the proportion of total saponins from ginseng roots is not less than that of total saponins from Panax notoginseng stems and leaves. In the combination of total saponins from American ginseng roots, total saponins from American ginseng stems and leaves, and total saponins from Panax notoginseng stems and leaves, the mass ratio of total saponins from American ginseng roots, total saponins from American ginseng stems and leaves, and total saponins from Panax notoginseng stems and leaves is preferably about 1:about 1:(1-2). The present invention does not limit the source of the total saponins of the original medicinal materials of Panax genus. It can be purchased from commercial channels or extracted from the original medicinal materials of Panax genus. The total saponins of the original medicinal materials of Panax genus extracted from the original medicinal materials of Panax genus are obtained by mixing the original medicinal materials of Panax genus and then preparing them using the method described above, or first preparing the total ginsenosides of each medicinal material separately using the method described above, and then mixing them to obtain the total ginsenosides of the original medicinal materials of Panax genus; the extraction method is to mix the original medicinal materials of Panax genus or extract each single medicinal material with 5-95% ethanol aqueous solution (preferably 50%-70%) by volume for 3 times or water percolation, or extract with other conventional extraction methods, and remove the solvent. The first extract is then extracted three times with n-butanol, and the n-butanol extract (the second extract) is separated by macroporous resin column chromatography and eluted with 30% and 70% ethanol aqueous solutions, the 70% ethanol eluate is collected, and the solvent is removed to obtain the 70% ethanol eluate (the third extract). Finally, the third extract is decolorized by macroporous ion exchange resin, eluted with deionized water, and the eluate is collected and concentrated to dryness to obtain the total ginsenosides from the original Panax genus medicinal material. The macroporous resin can be Diaion HP 20 or other commercial macroporous resin, and the mass ratio of the macroporous resin to the second extract is (8-10):about 1; the amount of the ethanol eluate is 3-5 column volumes.The macroporous ion exchange resin is D201 macroporous anion exchange resin or other decolorizing ion exchange resin. The mass ratio of the macroporous ion exchange resin to the third extract is (8-10): about 1; the amount of deionized eluent is 4-6 column volumes. The present invention has no special restrictions on the method for removing the solvent. The solvent removal method known in the art can be used. In the embodiment of the present invention, the solvent is recovered by reducing pressure. The mass volume ratio of the raw medicinal material of the genus Panax and 5-95% ethanol aqueous solution or water is 1g:20-30mL, more preferably 1g:25mL. In the embodiment of the present invention, the total saponins of American ginseng roots and the total saponins of American ginseng stems and leaves are both commercial products and homemade products, and the total saponins of ginseng roots, ginseng stems and leaves, and Panax notoginseng stems and leaves are all commercial products.

[0164] In the present invention, the solvent for dissolving the total saponins of the original medicinal material of Panax genus is preferably an ethanol aqueous solution with a volume percentage of about 30%; the mass volume ratio of the total saponins of the original medicinal material of Panax genus to the ethanol aqueous solution with a volume percentage of 30% is preferably 1 mg: 8 to 12 mL, more preferably 1 mg: 10 mL. 18 The silica gel chromatography column was balanced with an ethanol solution containing about 30% by volume. 18 The mass ratio of silica gel is preferably 1:7 to 10. 18 The specification of the silica gel chromatography column is preferably COSMOSIL 75C 18 -PREP filler.

[0165] In the present invention, when preparing the ginsenoside composition, an ethanol solution with a volume percentage of about 43% is preferably used for elution. During elution, the flow rate is preferably 150 to 200 mL / min. The eluate is collected and analyzed for each component in the eluate by HPLC. When ginsenoside Rb1 appears in the component, elution with the 43% ethanol solution is stopped. Elution is then continued with an ethanol solution with about 55%. The 55% ethanol eluate is collected to obtain each component, which is analyzed by HPLC until ginsenoside Rd no longer appears in the component. Elution with the 55% ethanol solution is stopped. Finally, the components containing Rb1, Rc, Rb2, Rb3, and Rd are combined and concentrated under reduced pressure to complete dryness to obtain a ginsenoside composition (PDSC). The content of each of the five ginsenosides in the ginsenoside composition (PDSC) is determined by HPLC, and the relative proportions of their contents and the total content of the five ginsenosides are calculated.

[0166] In the present invention, when preparing the holographic ginsenoside composition, it is preferred to use an ethanol aqueous solution with a volume percentage of about 30% for elution. During elution, the flow rate is preferably 150-200 mL / min. During elution, the eluate was collected and the components in the eluted solution were analyzed by high performance liquid chromatography (HPLC). When ginsenoside Rg1 appeared in the component, elution with about 30% ethanol aqueous solution was stopped, and then elution was continued with about 55% ethanol aqueous solution. The eluate with about 55% ethanol aqueous solution was collected to obtain the components, and the components were analyzed by HPLC until ginsenoside Rd no longer appeared in the component, and elution with about 55% ethanol aqueous solution was stopped. Finally, the eluate containing Rg1, Re, Rb1, Rc, Rb2, Rb3 and Rd was combined and concentrated under reduced pressure to complete dryness to obtain a holographic ginsenoside composition (HGC). The content of each of the seven ginsenosides in the holographic ginsenoside composition (HGC) was determined by HPLC, and the relative proportions of their contents and the total content of the seven ginsenosides were calculated.

[0167] In the present invention, the method for preparing the total ginsenoside composition comprises mixing the total saponins of Panax raw medicinal materials to obtain the total ginsenoside composition. The mixing scheme of the total saponins of Panax raw medicinal materials is the same as the mixing scheme of the total saponins when preparing the holographic ginsenoside composition, and will not be described in detail here.

[0168] The present invention provides the use of the ginsenoside composition or the ginsenoside composition prepared by the preparation method in preparing medicines for preventing and / or treating diseases or health products for exerting health care effects.

[0169] In the present invention, TGC, HGC, and PDSC all integrate the strengthening and revitalizing effects of Panax genus medicinal materials and the adaptogenic biological activity or pharmacological effects. The four ginsenosides (including Rb1, Rc, Rb3, and Rd) and their relative content configuration are the core supporting product functions. They can regulate homeostasis, including energy metabolism homeostasis, redox balance homeostasis, and neuroendocrine immune homeostasis, and improve the body's adaptive homeostasis capacity. Therefore, they can alleviate or even avoid harmful stress or events (also known as stressors, including physical, chemical / drug therapy, biological, and psychological harmful stressors) in the body and mind that deplete physical and psychological health reserves, leading to sub-health, disease, and accelerated aging. They can also adjust the neuroendocrine immune system state that has deviated from the physiological range back to the physiological range, thereby alleviating the symptoms of related diseases and promoting self-healing of diseases. Therefore, TGC has great application value in promoting health, and HGC and / or PDSC also have extensive medicinal value.

[0170] In the present invention, the extensive medicinal value of HGC and / or PDSC is based on a common mechanism. The results of the examples of the present invention have shown that the common mechanism of HGC and / or PDSC in treating various diseases includes the following: HGC and / or PDSC can protect and repair the functional and structural homeostasis of each member cell in the central neurovascular unit and peripheral similar functional units (hereinafter collectively referred to as functional units), thereby maintaining and rebuilding the microenvironmental homeostasis required for the healthy survival and effective work of the functional units (including but not limited to: energy, redox, NAD + , neurotransmitters), therefore, it can counteract or alleviate disease risk factors or / and pathogenic events from inside and outside the body that damage vulnerable members in the functional unit and trigger lesions in other members and subsequent pathological vicious cycles among members; it can also slow down or even cut off the pathological vicious cycles among members in the unit and repair the defects and damages, ultimately achieving the purpose of maintaining and repairing the functional and structural homeostasis of microvessels, glial cells, neurons and nerve fibers and realizing the medicinal value of preventing and treating nervous system diseases and delaying aging characterized by treating both the symptoms and the root causes.

[0171] In the present invention, the holographic ginsenoside composition and / or the ginsenoside composition are used in the preparation of a drug for preventing and / or treating a disease, which disease includes at least one of the following: a nervous system disorder, an autoimmune disease, a stress disease, aging and related diseases.

[0172] In the present invention, the neurological disorder preferably includes at least one of the following: psychiatric disorders, developmental delay and developmental disorders, nerve damage and functional disorders, neurodegenerative diseases, addictive diseases, and peripheral neuropathy. The psychiatric disorder preferably includes at least one of the following: schizophrenia, depression, bipolar disorder, anxiety disorder, and mania. The developmental delay and developmental disorder preferably includes at least one of the following: hyperactivity, inattention, learning disabilities, attention deficit hyperactivity disorder, autism, language disorders, sleep disorders, Tourette syndrome, and Tourette syndrome. The nerve damage and functional disorders preferably include at least one of the following: epilepsy, stroke, neuropsychiatric dysfunction, and akinesia sequelae. The neurodegenerative disease preferably includes at least one of the following: Parkinson's disease, Alzheimer's disease, vascular dementia, chorea, multiple sclerosis, and amyotrophic lateral sclerosis. The addictive disease preferably includes at least one of the following: alcohol and drug addiction, adolescent internet and gaming addiction, and pathological gambling. The peripheral neuropathy disease preferably includes at least one of the following: neuralgia, facial neuritis, hemifacial spasm, polyneuropathy, Guillain-Barré syndrome, neuralgia caused by viral infection, and movement disorders.

[0173] In an embodiment of the present invention, HGC or PDSC is used in the prevention and treatment of mental illness. Mental illness is characterized by hyperexcitability of striatal glutamate (Glu), insufficient inhibitory signals of γ-aminobutyric acid (GABA) and hyperexcited dopamine (DA) signals. The main functions of the basal ganglia include advanced cognitive functions such as motor control, reinforcement learning and emotional motivation. The striatum is the core of the basal ganglia, and its function is mainly regulated by excitatory input from the cerebral cortex and thalamus with Glu as the transmitter and DA input from the substantia nigra dopamine nerves and GABA transmitters from striatal interneurons. These transmitter signals are integrated with each other and output through spiny neurons to achieve regulation of cognition, emotion, motor function and habitual behavior. Hyperexcitability of striatal Glu, insufficient inhibitory signals of GABA and hyperexcited DA signals lead to mental illnesses including schizophrenia. At the same time, disorders of GABA inhibitory interneurons (PV-Ins) are also important pathological features of the above-mentioned neuropsychiatric diseases. Furthermore, astrocyte atrophy and loss of function are key features of most neuropsychiatric disorders and are the pathophysiological causes of schizophrenia, major depressive disorder (MDD), and bipolar disorder (BPD). Astrocytes are crucial for maintaining normal levels of extracellular Glu and GABA, and astrocyte atrophy and loss of function inevitably lead to hyperexcitability of Glu, further exacerbating the imbalance between excitatory and inhibitory functions caused by GABA function. Furthermore, psychiatric disorders are associated with disturbances in the gut microbiome. The HGC and PDSC compositions containing the two functional units "Rb1+Rd" and "Rc+Rb3" can protect damaged and normal function of astrocytes and inhibitory interneurons (PV-Ins), maintain or even reconstruct the balance of Glu excitatory and GABA inhibitory functions or neurochemical homeostasis in the striatum and other brain regions, and protect the healthy homeostasis of the gut microbiome, thereby targeting key links in the disease network to prevent and treat these neuropsychiatric disorders. Therefore, HGC and / or PDSC have application value and potential in preventing and treating these neuropsychiatric disorders.

[0174] In the embodiment of the present invention, HGC or PDSC is used in the prevention and treatment of epilepsy. The mechanism of HGC or PDSC containing two functional units of "Rb1+Rd" and "Rc+Rb3" in the prevention and treatment of epilepsy is as follows: (1) It can significantly inhibit the -aminobutyric acid (GABA) synthesis inhibitors isoniazid and thiocarbazide to induce acute epileptic seizures in rats. When used in combination with the existing anti-epileptic drug lamotrigine, it can greatly improve its anti-epileptic efficacy, which is prominently manifested in further reducing the severity of epileptic behavior and reducing the number of animals with major seizures; (2) HGC or PDSC used alone or in combination with lamotrigine can correct the hyperexcitability of chronic epileptic brain by increasing GABA and reducing glutamate, thereby returning to a physiological or near-physiological state of dynamic balance between central inhibition and excitability. Therefore, HGC and PDSC are closely related to lamotrigine. The combined use of HGC or PDSC and lamotrigine can not only overcome the serious defect of rebound seizures after lamotrigine discontinuation, but also produce sustainable anti-epileptic drug effects, with excellent efficacy of rapid onset, no drug tolerance, no rebound after discontinuation and sustained drug effects; (3) The combined use of HGC or PDSC and lamotrigine can completely counteract the serious side effects of dermatitis, neuropsychiatric disorders (such as irritable and aggressive behavior, anxiety, mental confusion, hallucinations, ataxia) and extrapyramidal adverse reactions (such as Parkinson-like or chorea-like movements) caused by lamotrigine in the treatment of epilepsy in mice; Therefore, HGC and PDSC alone or in combination with the anti-epileptic drug lamotrigine have application value and potential in the treatment of acute and chronic epilepsy and reducing the side effects of lamotrigine.

[0175] In an embodiment of the present invention, HGC and / or PDSC are used in the prevention and treatment of cerebral apoplexy. Since mitochondrial dysfunction, oxidative stress damage, and inflammatory response are closely related to acute stroke and chronic brain injury, the destruction and functional impairment of neurovascular units including cerebral vascular endothelial cells, astrocytes, and neurons are common pathological features of stroke. HGC and / or PDSC containing two functional units, "Rb1+Rd" and "Rc+Rb3", can protect cerebral vascular endothelial cells, astrocytes, and neurons from destruction and functional impairment, maintain ATP homeostasis to counteract mitochondrial dysfunction and the oxidative stress damage and inflammatory response caused by it, and PDSC and its related HGC can prevent epileptic seizures in the acute phase of cerebral ischemic injury in animals, quickly restore motor function damaged in the acute phase of ischemia-reperfusion, reduce mortality in the acute phase, and protect neurons in the ischemic brain area. Therefore, HGC and / or PDSC have application value and potential for the prevention and treatment of cerebral apoplexy.

[0176] In the embodiments of the present invention, the holographic ginsenoside composition (HGC) or the ginsenoside composition (PDSC) showed good efficacy in preventing and treating Parkinson's disease (PD). The two functional units "Rb1+Rd" and "Rc+Rb3" in HGC or PDSC can maintain and protect the cell energy metabolism homeostasis, redox homeostasis, mitochondrial function, oxidized coenzyme I (NAD + ) and glutathione (GSH) and reduced coenzyme II (NADPH)-mediated various physiological functions, promoting the regeneration of NADPH and GSH from their oxidized forms and increasing GSH synthesis to enhance the ability of endothelial cells with insufficient mitochondrial complex enzyme I function to scavenge reactive oxygen species (ROS), protecting the neurovascular unit including cerebral vascular endothelial cells, astrocytes and neurons, and inhibiting the formation of neurotoxic phenotype A1 cells, reconstructing the neurochemical homeostasis of glutamate (Glu) and -aminobutyric acid (GABA) in the animal striatum, maintaining the balance between central excitability and inhibition, and HGC or PDSC showed a significant therapeutic effect in the treatment of Parkinson's disease by haloperidol in mice by inhibiting dopamine receptor-induced stiffness symptoms, and in the treatment of Parkinson's disease in rats by rotenone, reflecting the treatment of Parkinson's disease. Furthermore, the combination of HGC or PDSC with the existing Parkinson's disease drug levodopa (L-DOPA) can significantly enhance L-DOPA's efficacy, reduce L-DOPA-induced dyskinesias, and prevent L-DOPA-induced schizophrenia, including reduced learning ability, neuropsychiatric and behavioral disorders, and delusions and hallucinations. Furthermore, changes in the gut microbiota, damage to the intestinal epithelial barrier, intestinal inflammation, and neuroplasticity reprogramming in the enteric nervous system are implicated in the pathophysiology of intestinal disorders in Parkinson's disease. HGC or PDSC can protect the gut microbiota against environmental toxicity, such as pesticides, or mitochondrial dysfunction, a risk factor for Parkinson's disease. This protective effect may also be a mechanism of action for HGC or PDSC in preventing and treating the development and progression of Parkinson's disease. These findings suggest that HGC or PDSC can be used to treat various symptoms of Parkinson's disease (PD), slow disease progression, enhance the efficacy of L-DOPA, and mitigate the severe toxic side effects associated with L-DOPA therapy.

[0177] In the embodiments of the present invention, since Alzheimer's disease, vascular dementia, chorea, multiple sclerosis and amyotrophic lateral sclerosis have the same pathological characteristics, including the destruction and functional impairment of neurovascular units including cerebral vascular endothelial cells, astrocytes and neurons, mitochondrial dysfunction accompanied by insufficient adenosine triphosphate (ATP) energy substances, oxidative stress damage and neuroinflammation, these pathological characteristics are closely related to the occurrence and development of the disease. The two functional units "Rb1+Rd" and "Rc+Rb3" contained in the HGC or PDSC can protect the destruction and functional impairment of cerebral vascular endothelial cells, astrocytes and neurons, maintain and protect mitochondrial function, maintain the energy substance ATP at a sufficient level, prevent and treat oxidative stress damage, inhibit the release of NF-B pathway and adhesion factors and inflammatory factors, and HGC or PDSC can prolong the lifespan of premature animals and significantly improve learning and memory abilities. Similarly, similar to PD, changes in the gut microbiome, damage to the intestinal epithelial barrier, and intestinal inflammation are closely associated with gastrointestinal diseases such as Alzheimer's disease, vascular dementia, chorea, multiple sclerosis, and ALS. HGC or PDSC can protect the homeostasis of the intestinal microbiome and inhibit inflammatory responses in patients. Therefore, HGC or PDSC have application value and potential in the prevention and treatment of Alzheimer's disease, vascular dementia, chorea, multiple sclerosis, and ALS.

[0178] In an embodiment of the present invention, HGC and / or PDSC are used in the prevention and treatment of addictive diseases. The lack of dopamine type 2 receptors (D2 receptors) causes individuals to have a variety of addictive, impulsive and compulsive behaviors, such as alcohol addiction, various drug and narcotic addiction, adolescent game addiction, pathological gambling, chronic violence and antisocial behavior. Consistently, alcohol and almost all medicines and drugs are to increase the release of dopamine to provide patients with physical and mental satisfaction. However, long-term dopamine overstimulation further weakens the originally low D2R receptor function and changes in the entire dopaminergic circuit, resulting in patients with stronger dependence and withdrawal symptoms on alcohol, drugs and narcotics. In addition, insufficient inhibitory function of aminobutyric acid (GABA) and hyperexcitability of glutamate (Glu) directly mediate withdrawal symptoms and are also closely related to gaming addiction. There are two main categories of drugs currently in use or in clinical trials for the prevention and treatment of the various addictions mentioned above: (1) acamprosate (a nonspecific GABA receptor agonist) and topiramate (activates type A GABA receptors), which promote GABA function; and (2) topiramate, lamotrigine, and gabapentin, which inhibit Glu excitatory signaling (inhibit presynaptic voltage-gated sodium and calcium channels, thereby inhibiting Glu release). HGC and / or PDSC products containing two functional units, "Rb1+Rd" and "Rc+Rb3," can directly counteract the effects of the D2 receptor inhibitor haloperidol, as well as the effects of chronic levodopa treatment that overstimulates D2 receptors, resulting in desensitization of some functions and hypersensitivity of others. They can also regulate excessively high Glu and GABA levels and low GABA levels in the striatum back to near physiological levels. Thus, HGC and PDSC can comprehensively regulate neurochemical abnormalities during addiction, during drug use, and during withdrawal, possessing the unique advantage of restoring brain homeostasis to normal (correcting D2 receptor dysfunction, GABA inhibition deficiency, and Glu excitability in individuals with addiction tendencies and patients, especially during withdrawal, returning them to or approaching normality). Therefore, HGC and PDSC may provide a new class of medications for the prevention and treatment of alcohol addiction, drug addiction, adolescent gaming addiction, pathological gambling addiction, sexual addiction, and various compulsive behaviors.

[0179] In an embodiment of the present invention, HGC and / or PDSC are used in the prevention and treatment of peripheral neuropathy. Although there are many causes of peripheral neuropathy, mitochondrial dysfunction is the main pathological mechanism of peripheral neuropathy. Specifically, mitochondrial dysfunction-mediated adenosine triphosphate (ATP) energy deficiency, oxidative stress and inflammatory response are all involved in the initiation and development of peripheral neuropathy. Currently, the most commonly used drugs for the treatment of peripheral neuropathy are the anticonvulsants gabapentin and pregabalin, whose mechanism of action is to block the voltage-gated sodium channels and calcium channels of the presynaptic terminals and downregulate the release of the excitatory neurotransmitter glutamate (Glu). In addition, vitamin B1, adenosylcobalamin and methylcobalamin, which are believed to be able to implement neurotrophic therapy, are also used to treat peripheral neuropathy caused by various reasons. Compared to existing drugs and technologies, HGC and / or PDSC, containing the two functional units of "Rb1+Rd" and "Rc+Rb3," possess unique effects and mechanisms of action: by protecting mitochondrial function, maintaining energy metabolism and redox homeostasis, preventing neuroinflammation, reducing Glu excitotoxicity, and enhancing GABA inhibitory function, they target the core pathological mechanisms of peripheral neuropathy, preventing the onset of disease and inhibiting its progression. Therefore, HGC and / or PDSC possess unique advantages and application value in the prevention and treatment of peripheral neuropathy.

[0180] In the present invention, the autoimmune disease preferably includes at least one of the following: allergic rhinitis, allergic asthma, urticaria, allergic conjunctivitis and autoimmune diseases caused by excessive immunity. The autoimmune disease caused by excessive immunity preferably includes at least one of the following: connective tissue disease, neuromuscular disease, digestive system disease, endocrine disease and urinary system disease. The connective tissue disease preferably includes at least one of the following: systemic lupus erythematosus-like, rheumatoid arthritis, dermatomyositis and scleroderma. The neuromuscular disease preferably includes at least one of the following: multiple sclerosis, myasthenia gravis and demyelinating disease. The digestive system disease preferably includes at least one of the following: chronic nonspecific ulcerative colitis, chronic active hepatitis, pernicious anemia and atrophic gastritis. The endocrine disease preferably includes at least one of the following: primary adrenal cortical atrophy and chronic thyroiditis. The urinary system disease preferably includes autoimmune glomerulonephritis and / or pulmonary hemorrhagic syndrome.

[0181] In the embodiments of the present invention, HGC and / or PDSC products containing two functional units of "Rb1+Rd" and "Rc+Rb3" can significantly inhibit the appearance of butterfly-shaped erythema on the cheeks of systemic lupus erythematosus (SLE) mice induced by the immunopotentiator pristane and reduce urine protein levels, and can completely inhibit the appearance of butterfly-shaped erythema on the cheeks of SLE mice when used in combination with the drug mycophenolate mofetil. Therefore, HGC and / or PDSC used alone or in combination with mycophenolate mofetil have advantages and application value in the treatment of systemic lupus erythematosus.

[0182] In the present invention, the stress-induced disease preferably includes chronic stress-induced diseases and / or stress-induced trauma sequelae. The chronic stress-induced disease preferably includes at least one of the following: cardiovascular disease, reproductive endocrine system disease, nervous system disease, and digestive system disease. The stress-induced trauma sequelae preferably includes at least one of the following: acute stress disorder, maladjustment, and post-traumatic stress disorder.

[0183] In the embodiment of the present invention, adaptive homeostasis enables biological systems to make continuous short-term adjustments in the ever-changing internal and external environment to achieve optimal function. The weakening of adaptive homeostasis response can weaken the resistance to various stressors (such as hypoxia, oxidative stress, immune response and psychological and mental stress). When the intensity and duration of the stress response caused by the stressor exceed the pressure that the body's adaptive homeostasis function can withstand, it will cause stress-related diseases (such as primary hypertension caused and aggravated by negative emotions, acute psychogenic reactions, delayed psychogenic reactions and adaptation disorders caused by stress, heart disease and autoimmune diseases caused by inflammation, viral infection and vaccination reactions caused by immunosuppression). While there is enough adenosine triphosphate (ATP) and oxidized coenzyme I (NAD + ) levels and appropriate NAD + The ATP and NAD / NADH ratio is crucial for maintaining cellular adaptive homeostasis. + Depletion of ATP will damage the cell's adaptive stress response, and ATP depletion will lead to depletion of reduced coenzyme II (NADPH) and glutathione (GSH) and inflammatory response. Since HGC and / or PDSC containing two functional units of "Rb1+Rd" and "Rc+Rb3" will not disrupt the cell's adaptive homeostasis, but will selectively activate the self-rescue mechanism of endothelial cells facing mitochondrial complex enzyme I deficiency, including moderately increasing NAD + Levels and NAD +The results of this study suggest that HGCs and PDSCs have significant medical value in preventing and treating these stress-related diseases by increasing the ratio of ATP to NADH (maintaining adequate ATP levels), promoting the regeneration of NADPH and GSH from their oxidized forms, and increasing GSH synthesis (enhancing the ability to scavenge ROS).

[0184] In the present invention, the aging and related diseases preferably include at least one of the following: senile constipation, hypertension, sleep disorders and chronic inflammation.

[0185] In the present invention, the dosage form of the drug preferably includes a liquid preparation and / or a solid preparation. The liquid preparation preferably includes an oral solution and / or an injection. The solid preparation preferably includes at least one of the following dosage forms: tablets, capsules, granules, pills, enteric-coated preparations, controlled-release preparations, and nanoformulations.

[0186] In the present invention, the total ginsenoside composition is preferably used in the preparation of health care products with health care effects.

[0187] In the present invention, the functions of TGC include improving metabolic status, nutritional status, neuroendocrine immune status, improving sleep, anti-oxidation, regulating intestinal flora, improving central growth and development, preventing premature aging and delaying aging. Therefore, TGC can help a wide range of people maintain good health and vitality, and can serve specific groups, including: young and middle-aged people with sub-health syndrome / physical and mental fatigue (such as physical fatigue, reduced mental work efficiency, impatience and negative emotions such as anxiety and depression) and sleep disorders, people who are under long-term psychological and social pressure, people with high three highs, people with insufficient immune system activity or autoimmune diseases (or stress diseases) , such as allergies and asthma, rheumatoid arthritis and lupus), patients who are facing or will face toxicity from anti-tumor treatment, people facing radiation hazards, people who receive long-term hormonal drugs (including glucocorticoids) or psychiatric drug treatment, children and adolescents with neuropsychiatric developmental delays and disorders, people with heart disease and hypertension, menopausal men and women with menopausal symptoms, people with skin diseases, people recovering from chronic diseases, people with premature aging, and elderly people with functional degeneration (including but not limited to: constipation, loss of appetite, memory loss, decreased immunity, slow movement, insomnia).

[0188] In the present invention, the health care effect preferably includes at least one of the following: drug treatment-induced side effects on the nervous system, delaying aging, and improving sub-health status.

[0189] In the present invention, the neurological side effects induced by drug therapy include neurological side effects caused by neuropsychiatric drugs or anti-tumor drugs. The neuropsychiatric drugs preferably include at least one of the following: dopamine receptor inhibitors and agonists, levodopa (L-DOPA), serotonin drugs, sodium and calcium channel inhibitors, glutamate receptor inhibitors, and other neurotransmitter receptor inhibitors. The anti-tumor drugs preferably include at least one of the following: chemotherapeutic drugs, molecular targeted drugs, and immunotherapy drugs.

[0190] In the present embodiment, levodopa treatment for Parkinson's disease often causes dyskinesias, and can also cause patients to experience schizophrenia symptoms such as reduced learning ability, psychoneurobehavioral disorders, and delusions and hallucinations. Combining HGC or PDSC with levodopa can significantly enhance the efficacy of levodopa, reduce levodopa-induced dyskinesias, and prevent levodopa-induced schizophrenia symptoms such as reduced learning ability, psychoneurobehavioral disorders, and delusions and hallucinations.

[0191] In the examples of the present invention, the existing anti-epileptic drug lamotrigine cannot prevent the occurrence of grand mal seizures in animals when used to treat epilepsy. However, the use of HGC or PDSC alone or in combination with lamotrigine can not only overcome the serious defect of rebound seizures after lamotrigine discontinuation, but also produce sustainable anti-epileptic efficacy, with rapid onset, no drug tolerance, and no rebound after discontinuation of the drug, but also can produce excellent efficacy. In addition, the combination of HGC or PDSC and lamotrigine can completely counteract the serious side effects of dermatitis, neuropsychiatric disorders (such as irritable and aggressive behavior, anxiety, mental confusion, hallucinations, ataxia), and extrapyramidal adverse reactions (such as Parkinsonian or choreiform movements) caused by lamotrigine treatment of epilepsy in mice.

[0192] In the present invention, the delaying of aging preferably includes at least one of the following: improving sleep, increasing appetite, activity and extending healthy life span of the elderly.

[0193] In the embodiment of the present invention, oxidized coenzyme I (NAD + ) deficiency can lead to mitochondrial dysfunction, adenosine triphosphate (ATP) deficiency and reactive oxygen species (ROS) accumulation, ultimately leading to high oxidative stress and cell senescence and death, while maintaining or restoring intracellular ATP and NAD + Levels and NAD + Keeping the ratio of Rb1 to Rd within the physiological range is a more effective anti-aging strategy than antioxidant and anti-inflammatory methods or targeting a specific mitochondrial functional molecule. HGC and / or PDSC containing two functional units, "Rb1+Rd" and "Rc+Rb3", can maintain and protect energy metabolism homeostasis, redox homeostasis, mitochondrial function and NAD +, various normal physiological functions mediated by glutathione (GSH) and reduced coenzyme II (NADPH), prolonging the lifespan of SAMP8 premature aging mice, and significantly improving the learning and memory abilities of SAMP8 premature aging mice and preventing the decline in learning and memory abilities of animals caused by chronic levodopa treatment. Therefore, HGC and PDSC have application value and potential in delaying aging.

[0194] In the present invention, the sub-health state preferably includes at least one of the following states: tension, sleep disorder, anxiety, depression, fear, memory loss and physical and mental fatigue.

[0195] In embodiments of the present invention, TGC achieves health benefits by improving sub-health conditions. Cellular adaptive homeostasis enables biological systems to make continuous short-term adjustments to constantly changing internal and external environments to achieve optimal function. A weakened adaptive homeostatic response can weaken resistance to various stressors. When the intensity and duration of the stress response triggered by a stressor exceeds the stress that the body's adaptive homeostatic function can withstand, it can cause various sub-health conditions, including emotional tension, sleep disorders, anxiety, irritability, anger, depression, memory loss, physical and mental fatigue, and reduced work efficiency. Adequate intracellular levels of adenosine triphosphate (ATP) and oxidized coenzyme I (NAD+), as well as a suitable NAD+ / NADH ratio, are crucial for maintaining cellular adaptive homeostasis. ATP and NAD+ depletion impairs cellular adaptive stress responses. ATP depletion also leads to depletion of reduced coenzyme II (NADPH) and glutathione (GSH), and inflammatory responses. Furthermore, a fragile intestinal flora and dysbiosis are also important contributors to sub-health conditions. Since the TGC containing the two functional units of "Rb1+Rd" and "Rc+Rb3" does not disrupt the adaptive homeostasis of cells, but selectively activates the self-rescue mechanism of endothelial cells facing mitochondrial complex enzyme I deficiency, including moderately increasing NAD+ levels and NAD+ / NADH ratios (maintaining ATP at a sufficient level), promoting the regeneration of NADPH and GSH from their oxidized forms and increasing GSH synthesis (improving the ability to scavenge ROS), it improves the ability of endothelial cells to cope with originally harmful stressors and can protect the healthy homeostasis of intestinal flora. Therefore, the results of the examples of the present invention support the health care use of the TGC in improving the sub-health state.

[0196] In the present invention, the health care product preferably includes a liquid health care product and / or a solid health care product. The liquid health care product preferably includes an oral liquid. The solid health care product preferably includes at least one of the following: a tablet, a capsule, a granule, and a pill.

[0197] The present invention provides a toxicity-reducing and efficacy-enhancing pharmaceutical composition, wherein the pharmaceutical active ingredients include a ginsenoside composition of ginsenosides and / or a holographic ginsenoside composition in the ginsenoside composition in combination with at least one of the following pharmaceutical active ingredients: Madopar (the mass ratio of levodopa to benserazide is 4:1), Sinimetics (the ratio of carbidopa to levodopa is 1:4), Darlingfor (50 mg of levodopa: 12.5 mg of carbidopa: 200 mg of entacapone), a dopamine type 2 receptor agonist, a dopamine receptor inhibitor, a chemotherapeutic drug or a target drug, a sodium and calcium ion channel inhibitor, and mycophenolate mofetil.

[0198] In the present invention, the dopamine receptor inhibitor preferably includes at least one of the following ingredients: haloperidol, olanzapine and risperidone. The sodium and calcium ion channel inhibitors preferably include lamotrigine or gabapentin. The combination of the drug prepared from the ginsenoside composition and / or the holographic ginsenoside composition with Western medicines such as dopamine receptor inhibitors in clinical practice can effectively improve the therapeutic effect, and make up for the defect of Western medicine in treating the symptoms but not the root cause (not correcting the disease), while also alleviating their side effects. In order to demonstrate the specific treatment plan after the ginsenoside composition and / or the holographic ginsenoside composition is used in combination with Western medicine, the following technical solution is specially proposed.

[0199] The present invention provides the use of a pharmaceutical composition for preparing a medicament for treating Parkinson's disease and / or alleviating the side effects of levodopa-induced Parkinson's disease treatment. The pharmaceutical composition comprises levodopa and at least one of the following compositions: a ginsenoside composition and a holographic ginsenoside composition. Combining the ginsenoside composition and / or the holographic ginsenoside composition with a levodopa-like drug to prepare a compound preparation effectively enhances efficacy and reduces toxicity. In this drug, HGC or PDSC plays a role in maintaining or reconstructing the homeostasis of non-dopamine neurotransmitters and dopamine receptor function in the striatum, and protecting the neurovascular unit. Levodopa is used to supplement the missing dopamine but at the same time disrupts the homeostasis of dopamine receptor function and non-dopamine transmitter homeostasis, especially causing a sharp and sustained increase in the level of the excitatory transmitter glutamate and a sharp and sustained decrease in the inhibitory transmitter γ-aminobutyric acid. The combined use of the two to treat Parkinson's disease can reconstruct the chemical homeostasis of the striatum close to that of normal people, thereby alleviating motor and non-motor symptoms, delaying or even blocking the progression of the disease, and slowing down or even eliminating the side effects of chronic levodopa treatment leading to dyskinesia, mental disorders and cognitive impairment.

[0200] The present invention provides the use of the pharmaceutical composition in the preparation of a drug for preventing and treating addictive diseases. The pharmaceutical composition includes a dopamine type 2 receptor agonist and at least one of the following compositions: a ginsenoside composition and a holographic ginsenoside composition. The ginsenoside composition and / or the holographic ginsenoside composition are combined with the dopamine type 2 receptor agonist to prepare a compound preparation, which can effectively achieve the effects of enhancing efficacy and reducing toxicity. In this drug, the dopamine type 2 receptor agonist combined with the ginsenoside composition or the holographic ginsenoside composition can effectively correct the insufficient γ-aminobutyric acid inhibitory signal and dopamine signal in the fragile brain (stimulation-seeking tendency) and the addicted brain, thereby achieving the purpose of preventing and treating addictive diseases.

[0201] The present invention provides the use of the pharmaceutical composition in the preparation of a drug for treating schizophrenia. The pharmaceutical composition includes a dopamine receptor inhibitor and at least one of the following compositions: a ginsenoside composition and a holographic ginsenoside composition. The ginsenoside composition and / or the holographic ginsenoside composition are used in combination with a dopamine receptor inhibitor to prepare a compound preparation, which can effectively achieve the effect of enhancing efficacy and reducing toxicity. In this drug, the dopamine receptor inhibitor alleviates the positive symptoms caused by dopamine signal hyperactivity by inhibiting dopamine type 2 receptors, but the inhibition of dopamine type 2 receptors leads to extrapyramidal reactions, namely PD-like motor symptoms. HGC or PDSC can not only make up for the defect of dopamine receptor inhibitors in having no efficacy in alleviating negative symptoms, but also prevent the occurrence of extrapyramidal reactions. Therefore, the combination of the two can achieve the effect of treating schizophrenia.

[0202] The present invention provides the use of the pharmaceutical composition in the preparation of a drug for treating tumors. The pharmaceutical composition includes a chemotherapy drug or a target drug and at least one of the following compositions: a ginsenoside composition and a holographic ginsenoside composition. The ginsenoside composition and / or the holographic ginsenoside composition are used in combination with a chemotherapy drug or a target drug to prepare a compound preparation, which can effectively achieve the effects of enhancing efficacy and reducing toxicity. In this drug, the chemotherapy drug or the target drug still plays a role in killing tumors, and HGC or PDSC not only alleviates the negative psychology caused by the patient's fear of the disease, but also alleviates the cardiotoxicity, neurotoxicity, immunotoxicity and fatigue caused by the anti-tumor drug. Therefore, the combined treatment of tumors with the two can achieve the drug effect of reducing toxicity and enhancing efficacy.

[0203] The present invention provides the use of a pharmaceutical composition for preparing a medicament for treating epilepsy, bipolar disorder, and conditions characterized by hyperglycemic Glu excitability or concurrent GABA inhibitory deficiency. The pharmaceutical composition comprises lamotrigine and at least one of the following compositions: a ginsenoside composition and a holographic ginsenoside composition. Combining the ginsenoside composition and / or the holographic ginsenoside composition with lamotrigine to prepare a compound preparation effectively enhances efficacy and reduces toxicity. In this drug, lamotrigine exerts its therapeutic effect by inhibiting Glu release, but also simultaneously inhibits GABA release. Chronic treatment can trigger the expression of additional ion channels in cells, leading to a gradual decrease in efficacy and rebound symptoms upon withdrawal, as well as common central nervous system side effects and severe dermatitis. HGC or PDSC can integrate the lamotrigine's inhibitory effect on Glu release and establish a new, stable balance between neural excitability and inhibition, resulting in a stronger and more stable therapeutic effect while avoiding the side effects of LTG. Therefore, the combined use of the two can achieve a toxicity-reducing and synergistic effect.

[0204] The present invention provides the use of a pharmaceutical composition for preparing a medicament for treating peripheral neuropathy or addictive diseases. The pharmaceutical composition comprises gabapentin and at least one of the following compositions: a ginsenoside composition and a holographic ginsenoside composition. Combining the ginsenoside composition and / or the holographic ginsenoside composition with gabapentin to prepare a compound preparation effectively enhances efficacy and reduces toxicity.

[0205] The present invention provides the use of a pharmaceutical composition for preparing a medicament for preventing or treating autoimmune diseases, skin diseases, or rejection reactions following liver and kidney transplantation. The pharmaceutical composition comprises mycophenolate mofetil and at least one of the following compositions: a ginsenoside composition and a holographic ginsenoside composition. Combining the ginsenoside composition and / or the holographic ginsenoside composition with mycophenolate mofetil to prepare a compound preparation effectively enhances efficacy and reduces toxicity.

[0206] In the present invention, the dosage forms of the drug preferably include oral preparations and injectable preparations. The oral preparations preferably include solid preparations and / or liquid preparations. The solid preparations preferably include at least one of the following dosage forms: capsules, conventional tablets, dispersible tablets, enteric-coated tablets, granules, pills, enteric-coated preparations, controlled-release preparations, and capsules containing micropellets or small tablets. The preparation method of the drug is not particularly limited in the present invention and can be prepared using methods known in the art. The administration method of the drug includes administering HGC or PDSC and the active pharmaceutical ingredient stepwise or preparing a composite formulation of HGC or PDSC and the active pharmaceutical ingredient. The dose (per day) of HGC or PDSC in the drug is preferably 25 mg to 200 mg, more preferably 50 mg to 100 mg, and the active pharmaceutical ingredient is 60% to 100% of the recommended dosage according to clinical prescriptions. In the composite formulation, the mass ratio of HGC or PDSC to the active pharmaceutical ingredient is 0.01 to 100:1, more preferably 0.1 to 10:1.

[0207] The present invention provides a preparation comprising the above ginsenoside composition or the ginsenoside composition prepared by the above preparation method, wherein the preparation comprises at least one of the following components: nutritional components and active components. The nutritional components include at least one of the following: proteins, polypeptides, glutathione precursor amino acids, NAD + The active ingredient comprises at least one of the following: a Chinese herbal extract or active ingredient that is both medicinal and edible, coenzyme Q10, vitamins, and energy metabolism intermediates.

[0208] In the present invention, the preparation preferably includes an oral preparation. The oral preparation includes a solid preparation and / or a liquid preparation. The solid preparation includes but is not limited to: capsules, ordinary tablets, dispersible tablets, enteric-coated tablets and granules. The present invention has no special restrictions on the preparation method of the health product, and the preparation method of health products well known in the art can be adopted. The weight of the total ginsenoside composition in the preparation is preferably 25 mg to 200 mg, more preferably 50 mg to 100 mg. The weight of the nutrients and active ingredients in the preparation is preferably the common dosage of each substance as a nutritional health product.

[0209] The following is a detailed description of a ginsenoside composition provided by the present invention, its preparation method and application, in conjunction with the examples. However, these examples should not be construed as limiting the scope of protection of the present invention.

[0210] Example 1. The contents of major ginsenotriol saponins and ginsenodiol saponins from ginseng roots and their stems and leaves, American ginseng roots and their stems and leaves, and Panax notoginseng stems and leaves are highly complementary.

[0211] The main active ingredients of traditional Chinese medicines derived from Panax plants, including ginseng root, stems, and leaves, American ginseng root, stems, and leaves, and Panax notoginseng and its stems and leaves, are various ginsenosides. However, each of these herbs is rich in its own dominant ginsenoside component, while also lacking (at low levels, <5%) or being absent (not detected under experimental conditions) certain other ginsenosides. Therefore, by combining these herbs, it is possible to prepare a holographic ginsenoside combination (HGC) with superior biological activity and pharmacological effects compared to ginsenoside combinations derived from these single herbs. Based on this, the high-performance liquid chromatography (HPLC) method specified under the Chinese medicinal ginseng section in the Pharmacopoeia of the People's Republic of China (Volume 1, page 9, 2020 edition) was used to determine the contents of ginsenoside Rg1 (abbreviated as Rg1) and ginsenoside Re (abbreviated as Re), as well as ginsenoside Rb1 (abbreviated as Rb1), ginsenoside Rb2 (abbreviated as Rb2), ginsenoside Rb3 (abbreviated as Rb3), ginsenoside Rc (abbreviated as Rc), and ginsenoside Rd (abbreviated as Rd) in commercial ginsenosides from 2020, including total saponins from Panax ginseng roots, total saponins from Panax ginseng stems and leaves, total saponins from American ginseng roots, total saponins from American ginseng stems and leaves, and total saponins from Panax notoginseng stems and leaves. To further refine the individual characteristics of the main ginsenosides contained in each medicinal material, the relative contents of ginsenosides to ginsenosides, as well as the relative contents of different individual components, were analyzed.

[0212] The results of HPLC analysis are shown in Tables 1 and 2.

[0213] Table 1 Contents of major ginsenotriol saponins and ginsenodiol saponins in total saponins from different medicinal materials of Panax genus (%, n=3)

[0214] The total saponins of ginseng root contain 11.97% of total ginsenosides of panaxatriol (Re / Rg1=2.43) and 52.92% of total ginsenosides of panaxadiol (Rb1 / Rc / Rb2 / Rb3 / Rd=1.12 / 1.00 / 0.78 / 0.17 / 0.58). The saponins with high content (10-19%) include Rb1 (16.18%), Rc (14.50%) and Rb2 (11.36%), the saponins with medium content (5-9%) include Re (8.48%) and Rd (8.39%), and the saponins with low content (<5%) include Re (3.49%) and Rd (2.49%). The total saponins in ginseng stems and leaves contain 34.86% of total ginsenosides of panaxatriol (Re / Rg1=2.41) and 32.32% of total ginsenosides of panaxadiol (Rb1 / Rc / Rb2 / Rb3 / Rd=1.38 / 1.00 / 1.17 / 0.35 / 3.26). The saponins with extremely high content (≥20%) include Re (24.62%), the saponins with high content (10-19%) include Rd (14.71%) and Rg1 (10.23), the saponins with medium content (5-9%) include Rb1 (6.21%) and Rb2 (5.28%), and the saponins with low content (<5%) include Rc (4.51%) and Rb3 (1.59%).

[0215] The total saponins of American ginseng root contain 15.21% of total ginsenosides of panaxatriol (Re / Rg1=6.96) and 59.10% of total ginsenosides of panaxadiol (Rb1 / Rc / Rb2 / Rb3 / Rd=3.26 / 1.00 / 0.34 / 0.33 / 1.12). The saponins with extremely high content (≥20%) include Rb1 (31.95%), the saponins with high content (10-19%) include Re (13.30%) and Rd (11.01%), the saponins with medium content (5-9%) include Rc (9.81%), and the saponins with low content (<5%) include Rb2 (3.38%), Rb3 (3.28%) and Rg1 (1.91%). The total saponins from American ginseng stems and leaves contain 22.46% of total ginsenosides of panaxatriol (Re / Rg1=2.74) and 40.16% of total ginsenosides of panaxadiol (Rb1 / Rc / Rb2 / Rb3 / Rd=1.07 / 1.00 / 1.52 / 1.93 / 3.82). The saponins with high content (10-19%) include Re (16.45%) and Rd (16.42%), the saponins with medium content (5-9%) include Rb3 (8.32%), Rb2 (6.52%) and Rg1 (6.00%), and the saponins with low content (<5%) include Rb1 (4.60%) and Rc (4.30%).

[0216] The total saponins in the stems and leaves of Panax notoginseng contain 46.78% of total ginsenosides (Rb1 / Rc / Rb2 / Rb3 / Rd=0.26 / 1.00 / 0.26 / 1.28 / 0.17). The saponins with extremely high content (≥20%) include Rb3 (20.15%), the saponins with high content (10-19%) include Rc (15.72%), the saponins with low content (<5%) include Rb1 (4.13%), Rb2 (4.08%) and Rd (2.71%), and the ginsenosides Rg1 and Re are lacking.

[0217] Table 2 The main active ingredients of ginsenosides in different medicinal materials of Panax genus are complementary.

[0218] The above analysis results show that the contents of the seven main ginsenosides contained in each medicinal material and the relative proportions of their contents are very different. There is no doubt that the content characteristics of the seven ginsenosides analyzed above support the efficacy and existing clinical uses of each medicinal material, and also suggest that the individual components of the ginsenosides derived from these medicinal materials may not be able to effectively exert the full biological activity and pharmacological effects of ginsenotriol saponins and ginsenodiol saponins and their related health care and medical uses. However, there is a good complementary relationship between the individual components of the ginsenosides derived from ginseng roots, ginseng stems and leaves, American ginseng roots, American ginseng stems and leaves, and Panax notoginseng stems and leaves, and such a complementary relationship can be used to prepare a holographic ginsenoside composition (HGC) rich in active ingredients Rg1, Re, Rb1, Rc, Rb2, Rb3, and Rd.

[0219] Ginsenosides Rg1, Re, Rb1, Rc, Rb2, Rb3, and Rd possess a wide range of biological activities, including metabolic regulation, neuroendocrine and immune activities, and neuroprotection. They also possess a broad range of pharmacological effects, including antioxidant and anti-inflammatory properties, and protection of cells such as nerves, cardiomyocytes, and vascular endothelial cells from internal and external pathogenic factors. Therefore, integrating these active ginsenosides to form a composition containing these major ginsenoside triol and ginsenodiol active ingredients could potentially represent a combination of active ginsenosides that encompasses and surpasses the health and medical benefits of ginseng roots, stems, and leaves, American ginseng roots, stems, and leaves, and Panax notoginseng stems and leaves.

[0220] Therefore, the present invention attempts to comprehensively utilize the above-mentioned Panax genus medicinal materials to prepare a holographic ginsenoside composition (HGC) containing the main active ginsenosides panaxtriol saponins and diol saponins. However, to prepare such an active composition (HGC), it is first necessary to clarify the content ratio between panaxtriol saponins and ginsenodiol saponins; secondly, it is necessary to understand that central hyperexcitability and / or inhibitory dysfunction are closely related to the expression of clinical symptoms and disease progression of Parkinson's disease (PD), as well as to the occurrence and development of other neurodegenerative diseases including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). The effect of panaxtriol saponins in promoting central excitability is not conducive to the efficacy of the holographic ginsenoside composition in preventing and treating PD and other neurodegenerative diseases, and may also antagonize the effect of panaxdiol saponins in the composition in promoting central inhibition, thereby weakening the efficacy of the composition. However, both panaxatriol saponins and panaxadiol saponins have been reported to have antioxidant, anti-inflammatory, and neuroprotective pharmacological effects, suggesting that the combined use of these two saponins may have greater efficacy than either alone. Therefore, finding the appropriate ratio of the two saponin components when combined is crucial for ensuring that the holographic ginsenoside composition integrates the pharmacological effects of both components, thereby enhancing their respective medicinal value. To determine the appropriate ratio of the two components in the composition, studies in Examples 2 and 3 were conducted.

[0221] Example 2. A ginsenoside composition and a triol saponin composition were prepared according to a ratio of 1 part of total saponins from roots of American ginseng and 2 parts of total saponins from stems and leaves of American ginseng.

[0222] According to the results of Example 1, the total saponins of American ginseng roots and total saponins of American ginseng stems and leaves commercialized in 2020 were first comprehensively utilized in a weight ratio of (1:2) to feed, and the ginsenoside combination (Panaxadiol saponins combination, PDSC1) and the ginsenoside combination (Panaxatriol saponins combination, PTSC1) were separated and prepared by conventional methods. HPLC determination data showed that PDSC1 contained five ginsenosides, Rb1, Rc, Rb2, Rb3, and Rd, and the total content of these five components was 93.03%, while PTSC1 mainly contained ginsenosides Rg1 and Re, and the total content of these two saponins was 91.01%. The content of each individual ginsenoside is shown in Table 3.

[0223] Table 3 Content of the main individual components of PDSC1 and PTSC1 (%, n=3)

[0224] Example 3. Exploring the compatibility rules of holographic ginsenoside composition (HGC) with pharmacological effects.

[0225] Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease (AD), and animal models are more established than for other neurodegenerative diseases. Therefore, the efficacy of PDSC1 and PTSC1, as well as complexes of the two at varying dosage ratios, in treating PD was first investigated using two internationally recognized models to clarify their efficacy and the impact of interactions on efficacy. These two models are a mouse model of rigidity induced by the antipsychotic drug haloperidol (HAL) through inhibition of dopamine receptors, and a rat model of Parkinson's disease induced by rotenone (ROT) through inhibition of mitochondrial complex I. These models, respectively, reflect the palliative and fundamental effects of the test drugs on PD. The former can simulate the motor symptoms of PD patients caused by insufficient dopamine signaling and is often used to evaluate the symptomatic efficacy of test drugs. It can also reflect the non-dopaminergic mechanisms of drug efficacy. Therefore, a positive efficacy indicates that the test drug can control or alleviate PD motor symptoms, especially in late-stage PD and atypical PD that are insensitive to dopamine drugs. It can also indicate that the test drug can control or alleviate PD-like motor symptoms caused by drug therapy, especially antipsychotic drugs, i.e., the efficacy of therapeutic PD syndrome. The ROT model closely simulates the development, progression, and clinical characteristics of PD in terms of pathogenic factors, pathogenic mechanisms, and symptoms and signs. Therefore, it is often used to evaluate the efficacy of drugs in preventing and treating the development and progression of PD, that is, their effect on the root cause of PD, as well as to study the drug's mechanism of action.

[0226] Example 3-1. The efficacy of PTSC1 in counteracting or assisting PDSC1 in alleviating motor symptoms of PD depends on the relative ratio of the two.

[0227] The efficacy of the test drug was evaluated using a conventional HAL-induced stiffness model in mice. In summary, adult male ICR mice weighing 24 ± 2 g, acclimated for 3–4 days, were trained on a pole once daily for four consecutive days to ensure that each animal had mastered the pole climbing task. Pre-modeling stiffness parameters were assessed on the fifth day, including the time it took for the mouse's head to rotate from an upward position to a downward position on the pole (Tturn) and the time it took to completely descend from the pole to the ground (Ttotal). The test was completed within 90 seconds; failure to complete the task within 90 seconds was considered a 90-second data point. The test drug was then administered orally, and HAL (2 mg / kg) was injected intraperitoneally 45 minutes later. The pole climbing test was repeated between 45 and 90 minutes after HAL administration to obtain experimental parameters for the model and test drug groups.

[0228] The experimental results (Table 4) showed that PDSC1 antagonized the occurrence of stiffness symptoms induced by HAL (2 mg / kg) in a dose-dependent manner. Specifically, the low dose (40 mg / kg) showed a pharmacodynamic trend (*p<0.05), while the medium dose (60 mg / kg) and high dose (80 mg / kg) both had very significant pharmacodynamics (***p<0.001).

[0229] Table 4 Effect of Panaxadiol Saponin Composition (PDSC1) on Anti-Haloperidol (HAL)-Induced Rigidity (mean ± SEM, n = 8) Note: One-way ANOVA was used to analyze the experimental data. Compared with the HAL group before HAL administration, &&& p<0.001; compared with the HAL group after HAL administration, *p<0.05, ***p<0.001.

[0230] However, the PTSC1 combination failed to antagonize HAL-induced rigidity at doses of 30 mg / kg and 60 mg / kg, and instead showed a tendency to exacerbate rigidity (Table 5). Further observations were made in animals receiving both an effective dose of PDSC1 and varying doses of PTSC1 to combat HAL-induced rigidity, to determine whether PTSC1 weakened the efficacy of PDSC1 in alleviating HAL-induced rigidity, or whether the two could be used together within a specific dosage range. The mixed administration regimen includes: (1) HAL (2 mg / kg) + PDSC1 (60 mg / kg, optimal effective dose) + PTSC1 (60 mg / kg), (2) HAL (2 mg / kg) + PDSC1 (60 mg / kg) + PTSC1 (20 mg / kg), (3) HAL (2 mg / kg) + PDSC1 (30 mg / kg) + PTSC1 (30 mg / kg) (total saponins 60 mg / kg), in order to determine the efficacy of the two saponin compositions, each with an ineffective dose and a total saponin dose equivalent to the optimal dose of PDSC1. The experimental results are shown in Table 5. When a low dose of PTSC1 (20 mg / kg) was mixed with the optimal dose of PDSC1 (60 mg / kg), PTSC1 could weaken the efficacy of PDSC1 ( # p<0.05), a medium dose of PTSC1 (30 mg / kg) was mixed with an equal dose of PDSC1 (30 mg / kg), and PTSC1 significantly weakened the efficacy of PDSC1 ( ## p<0.01), while high dose of PTSC1 (60 mg / kg) was mixed with the optimal dose of PDSC1 (60 mg / kg), and PTSC1 almost completely offset the efficacy of PDSC1 ( ## p<0.01).

[0231] Based on this, the effects of a series of low doses of PTSC1 on the efficacy of the optimal dose of PDSC1 (60 mg / kg) were further determined, including the administration of PTSC1 at doses of 1 / 2, 1 / 3, 1 / 4, 1 / 5 and 1 / 6 of the optimal dose of PDSC1 (60 mg / kg) and the optimal dose of PDSC1 mixture, in order to clarify whether there is a suitable ratio of ginsenoside composition for the efficacy when ginsenoside diols are the dominant composition of the holographic saponin composition. The experimental results (Table 6) show that when the PTSC1 / PDSC1 (1 / 2) mixture is administered, its efficacy against mouse stiffness is equivalent to that of the optimal dose of PDSC1, indicating that the mixture containing one-third of PTSC1 will not affect the efficacy of PDSC1 in treating PD. However, when the PTSC1 / PDSC1 (1 / 3) mixture is administered, PTSC1 significantly weakens the efficacy of PDSC1 ( & p<0.05), and other lower ratios of PTSC1 would not significantly weaken the efficacy of PDSC1.

[0232] Table 5 Effects of Panaxatriol Saponin Composition (PTSC1) on Haloperidol (HAL)-induced Rigor Mortis (mean ± SEM, n = 8) Note: One-way ANOVA was used to analyze the experimental data. Compared with the HAL group before HAL administration, &&& p<0.001; compared with the HAL group after HAL administration, *** p<0.001; compared with the HAL+PDSC1(2+60) group after HAL administration, # p<0.05, ## p<0.01.

[0233] Table 6 Effect of low-dose ginsenoside composition (PTSC1) on the efficacy of optimal-dose ginsenoside composition (PDSC1) against stiffness symptoms (mean ± SEM, n = 10) Note: One-way ANOVA was used to analyze the experimental data. Compared with the HAL group before HAL administration, *** p<0.001; Compared with the HAL group after HAL administration, # p<0.05, ## p<0.01, ### p<0.001; compared with HAL+PDSC1 group, & p<0.05.

[0234] Finally, the efficacy of a series of PDSC1 and PTSC1 mixtures (in which PDSC1 was the predominant content, and the total dose of the two combinations was 60 mg / kg) was further tested to determine whether one or more specific holographic ginsenoside combinations could replace PDSC1 in combating HAL-induced rigidity. The results, shown in Table 7, show that the efficacy of the mixtures containing PTSC1 at doses of 10 mg / kg and 12 mg / kg was weaker than that of the PDSC1 control. As the PTSC1 content in the mixtures increased, their efficacy further decreased until they were completely ineffective.

[0235] Based on the results of the above examples, it can be seen that the ginsenoside composition (PDSC1) can significantly counteract the stiffness of mice induced by HAL, and can therefore be used as an effective medicinal form of ginsenosides to alleviate the motor symptoms of PD. The ginsenoside composition (PTSC1) cannot counteract the stiffness of mice induced by HAL, but instead tends to aggravate the stiffness. An equal dose of PTSC1 can completely cancel the efficacy of PDSC1, and a dose of PTSC1 lower than PDSC1 will also weaken the efficacy of PDSC1, but there is an exception, that is, when the ratio of PTSC1 / PDSC1 is 1 / 2, PTSC1 does not interfere with the efficacy of PDSC1. It can be seen that the interaction between PTSC1 and PDSC1 or the ratio of their content on the efficacy of the holographic ginsenoside composition is not a linear relationship. This discontinuous jump-like change breaks the conventional understanding of those skilled in the art. Importantly, this unconventional discovery can not only guide us to scientifically use the efficacy of ginseng and Panax genus, but also inspire us to further explore the medicinal value of ginsenosides.

[0236] It is worth noting that the weight ratio of PDSC1 to PTSC1, obtained by mixing total saponins from American ginseng roots and stems and leaves at a ratio of 1:2 by weight, is 2.18. Therefore, we believe that a holographic ginsenoside composition based on its natural ratio is also an effective medicinal form for treating PD symptoms, a concept that will be verified in subsequent studies.

[0237] Table 7 Pharmacological efficacy of holographic ginsenosides with PDSC as the dominant composition against haloperidol (HAL)-induced stiffness in mice (mean ± SEM, n = 10) Note: One-way ANOVA was used to analyze the experimental data. Compared with the HAL group before HAL administration, *** p<0.001; compared with the HAL group after HAL administration, # p<0.05, ## p<0.01, ### p<0.001; compared with HAL+PDSC1 group, & p<0.05, && p<0.01,&&& p<0.001.

[0238] Example 3-2. The efficacy of PTSC1 in counteracting or assisting PDSC1 in counteracting the occurrence and development of PD depends on the relative ratio of the two.

[0239] Methods: A PD model was induced in rats by subcutaneous injection of rotenone (ROT) in the back and gradually increasing the dose. The therapeutic effect of the test drug was evaluated by weight loss, PD clinical behavioral sign scores, forelimb ability, and motor balance ability. The degeneration of the nigrostriatal dopamine neural pathway was further determined in representative test groups.

[0240] Modeling method and disease severity assessment: Rotenone injection starts at a low dose, and the dose is increased by 25% every 5 days, once in the morning and evening. The specific method is as follows: the modeling dose for the first 5 days is 0.5 mg / kg, the dose is increased to 0.625 mg / kg for the second 5 days, and the modeling dose for the third 5 days is 0.75 mg / kg. The volume of each administration is 0.2 mL / 100 g, once in the morning (8:30 am) and once in the evening (20:30 pm). The experiment stipulates that when the model animals show behavioral symptoms of level 4 or above, the injection of rotenone is stopped. If there are still rats that have not reached level 4 behavioral performance after the third 5 days, the modeling will continue according to the dosage of the third 5 days. Most animals usually show level 3 or above PD behavior within 12 to 15 days.

[0241] The classification of clinical behavioral signs in the PD model is divided into 6 levels. Level 1: resisting arrest, erect hair, yellowing and dirty fur, arched back, weakened behavior, and reduced main activities; Level 2: presenting the symptoms of level 1, but with a significant reduction in main activities, slow movements, and tremors and unstable gait; Level 3: presenting the symptoms of level 2, with an unstable gait or inability to walk in a straight line, or rotating to one side while walking; Level 4: unilateral recumbency, unilateral forelimb or hindlimb paralysis, difficulty walking, and difficulty eating; Level 5: unilateral recumbency, limb cramps, and significant weight loss; Level 6: impending death or death.

[0242] Forelimb raising test (RT): After the rat is placed in a black, opaque cylindrical bucket, a timer is started and video recorded over a 5-minute period to measure the number of times the rat raises its forelimbs. A forelimb raising test is performed if one or both forelimbs are raised above the shoulder and in contact with the bucket wall, and then lowered completely to the bottom of the bucket.

[0243] For the FAS test (Fast Stride Assessor), the experimenter holds the rat's hind limbs with one hand, while securing the right forelimb. The rat's left forelimb is placed on the ground, with the body at a 45-degree angle to the tabletop, ensuring that the full weight of the rat rests on the left forelimb. The rat is then moved forward along the edge of the table at a constant speed of 90 cm per 10 seconds. The number of times the rat lifts its left forelimb to maintain balance during the 10-second movement is recorded. The test is repeated three times for each rat, with 5-second intervals between each test. The average of these three measurements is used.

[0244] Rotarod test: Set the rat fatigue rotarod instrument to a speed of 15 rpm for 2 minutes. After the instrument accelerates to the set speed, place the rat on the rotarod with its head facing the opposite direction of the rotarod's rotation and all four limbs attached to the rotarod. Record the time the rat spends on the rotarod, as indicated by the instrument's automatic stop timer. Each rat is tested three times, with an average value taken as the measured value, with a 2-minute interval between each test. The forelimb lift and stride tests reflect the motor function of the animal's forelimbs, while the rotarod test reflects the motor function of the animal's limbs and overall motor coordination.

[0245] Experimental Grouping, Dosing, and Drug Efficacy Observation: Adult male Sprague-Dawley rats, weighing 280-320 g, were randomly divided into a normal group, a rotenone (ROT) model group, and a test drug-treated group after acclimation. The test drug was administered orally once daily, at the prescribed dose, in the morning (8:30 am) and evening (8:30 pm), 1 hour before ROT administration. Each dose was half the daily dose, with a volume of 0.2 mL / 100 g. The normal control and ROT model control groups received an equal volume of normal saline. Body weight and clinical behavioral signs of PD were monitored daily. The three motor behavioral tests described above were performed at designated time points to assess the efficacy of the test drug against ROT-induced PD. Rotenone administration was discontinued when the PD behavioral score of the model group reached level 3. Various motor behavioral indicators were collected on the same day and 48 hours later. Brain tissue was fixed with paraformaldehyde by cardiac perfusion for analysis of degeneration of the nigrostriatal dopamine neuronal pathway. At the same time, an equal number of animals in each drug treatment group were treated in parallel, starting with the animals with the highest motor behavior score.

[0246] Based on the research results of Example 3-1, the first test drugs observed included three dose groups of PDSC1 (20, 40 and 60 mg / kg) and three dose groups of PTSC1 at corresponding doses. The research results are shown in Table 8. PDSC1 has a dose-dependent effect against rotenone-induced PD in rats. The dose-effect relationship is a common inverted U-shaped dose-effect relationship, showing that the middle dose (40 mg / kg) shows the best effect on all the indicators measured, and the effective dose range is between 40 and 60 mg / kg. However, the efficacy of PTSC1 is only comparable to that of the same dose of PDSC1 at 40 mg / kg, while other doses are ineffective. It can be seen that the effective dose range of PDSC1 against rotenone-induced PD formation is wider than the effective dose range of PTSC1.

[0247] Next, the efficacy of the optimally effective dose of the two combined, as well as the optimal dose of PDSC1 combined with half the dose of PTSC1, was examined to validate the findings in the HAL-induced stiffness mouse model. As shown in Table 8, no significant efficacy was observed when both were administered at a dose of 40 mg / kg, indicating that an equal dose of PTSC1 significantly counteracted the efficacy of PDSC1. Furthermore, when 40 mg / kg of PDSC1 was combined with 20 mg / kg of PTSC1, PTSC1 did not significantly diminish the efficacy of PDSC1. This suggests that a holographic ginsenoside composition composed of equal proportions of PDSC1 and PTSC1 lacked efficacy against the development and progression of PD. However, a holographic ginsenoside composition composed of two parts PDSC1 and one part PTSC1 demonstrated comparable efficacy to an equal dose of PDSC1. Consistent with its efficacy in treating PD symptoms, these results demonstrate that a holographic ginsenoside composition composed of panaxadiol soaps in their natural proportions is also an effective medicinal form for treating the root cause of PD.

[0248] Table 8 Effects of PDSCs, PTSCs and their combination on rotenone (ROT)-induced PD formation in rats Note: One-way ANOVA was used to analyze the experimental data. *** p<0.001; compared with ROT group, ## p<0.01, ### p<0.001; compared with PDSC1 (40 mg / kg) group, & p<0.05.

[0249] Combined results from the two models above indicate that a holographic ginsenoside composition (HGC) constructed with a 2:1 ratio of PDSC1 to PTSC1 exhibits comparable pharmacological activity against both the root causes and symptoms of PD, as does an equivalent dose of PDSC1. Therefore, it will be referred to as a holographic ginsenoside composition (HGC). From a Traditional Chinese Medicine (TCM) perspective, the panaxatriol saponin composition (PTSC) underlies the seven-part yang properties of ginseng, while the panaxadiol saponin composition (PDSC) underlies its three-part yin properties. Therefore, HGC represents a yin-yang combination, with yin being the dominant factor. PD, a disease whose pathogenesis and symptom expression are closely linked to hyperexcitatory and inadequate inhibitory function, weakens excitatory acetylcholine signaling with prolonged disease course, necessitating long-term medication. Therefore, HGC represents a scientific, safe, and effective medicinal approach, both from the perspectives of TCM theory and modern medicine. Furthermore, HGC reduces the amount of ginsenosides required by approximately one-third, significantly reducing resource consumption of the original medicinal material. Clearly, compared to the medicinal use of total saponins, diol saponin combinations, or individual saponins, HGC is not only a novel approach, but also a novel method of use that utilizes precious medicinal resources with low consumption and high efficacy. More importantly, the PTSC / PDSC ratio in HGC and the content configuration of its main active ingredients, Rg1, Re, Rb1, Rc, Gb2, Rb3, and Rd, provide a feedstock basis and product quality standards for the subsequent comprehensive utilization of ginseng, American ginseng, and Panax notoginseng to prepare holographic ginsenoside compositions.

[0250] Example 3-3. The content configuration of the main individual components of the holographic ginsenoside composition (HGC) was determined to clarify the content configuration of the main active individual components of the superior composition.

[0251] Based on this, HPLC analysis was used to determine the content of total saponins, panaxatriol saponins, and panaxadiol saponins in holographic ginsenoside compositions (HGCs) containing different ratios of PDSC1 and PTSC1, as well as the content and configuration of the seven saponins. The relationship between content and efficacy was intuitively analyzed using the HAL and ROT models. The experimental results are shown in Table 9, and these experimental data will serve as guiding indicators for the subsequent preparation of HGCs.

[0252] Table 9 Relationship between the content of main components of holographic ginsenoside composition (HGC) and its efficacy Note: TPDS: total ginsenosides; TPTS: total ginsenosides; + corresponds to p < 0.05, ++ corresponds to p < 0.01, +++ corresponds to p < 0.001; a Narrow dosage range.

[0253] Example 4. Preparation of Holographic Ginsenoside Composition (HGC) by Comprehensive Utilization of Panax ginseng, American ginseng and Panax notoginseng

[0254] According to the guiding parameters of the HGC content configuration and the content data of the seven ginsenosides described in the total saponins of ginseng roots and stems and leaves, total saponins of American ginseng roots and stems and leaves, and total saponins of Panax notoginseng stems and leaves obtained in Example 1, the following 10 feeding schemes were designed to prepare 10 holographic ginsenoside composition samples (HGC1 to HGC10): (1) from the mixture of "1 part of total saponins of American ginseng roots + 2 parts of total saponins of American ginseng stems and leaves", Prepare HGC1, (2) prepare HGC2 from a mixture of "1 part total saponins from ginseng roots + 1 part total saponins from American ginseng roots + 1 part total saponins from ginseng stems and leaves + 3 parts total saponins from American ginseng stems and leaves", (3) prepare HGC3 from a mixture of "2 parts total saponins from ginseng roots + 1 part total saponins from ginseng stems and leaves + 1 part total saponins from Panax notoginseng stems and leaves", (4) prepare HGC3 from a mixture of "2 parts total saponins from ginseng roots + 1 part total saponins from ginseng stems and leaves + 2 parts total saponins from Panax notoginseng stems and leaves". (5) HGC5 was prepared from a mixture of "1 part total saponins from ginseng roots + 1 part total saponins from ginseng stems and leaves + 1 part total saponins from Panax notoginseng stems and leaves", (6) HGC6 was prepared from a mixture of "1 part total saponins from ginseng roots + 1 part total saponins from ginseng stems and leaves + 2 parts total saponins from Panax notoginseng stems and leaves", and (7) HGC7 was prepared from a mixture of "2 parts total saponins from American ginseng roots + 1 part total saponins from American ginseng stems and leaves + 1 part total saponins from Panax notoginseng stems and leaves". , (8) HGC8 was prepared from a mixture of "2 parts of total saponins from American ginseng roots + 1 part of total saponins from American ginseng stems and leaves + 2 parts of total saponins from Panax notoginseng stems and leaves", (9) HGC9 was prepared from a mixture of "1 part of total saponins from American ginseng roots + 1 part of total saponins from American ginseng stems and leaves + 1 part of total saponins from Panax notoginseng stems and leaves", (10) HGC10 was prepared from a mixture of "1 part of total saponins from American ginseng roots + 1 part of total saponins from American ginseng stems and leaves + 2 parts of total saponins from Panax notoginseng stems and leaves".

[0255] The specific preparation method is as follows: 30 g of each mixture described in the feeding scheme is dissolved in 300 ml of 30% ethanol aqueous solution, and the mixture is loaded on a reverse phase C 18Silica gel (ODS, 300 g) chromatography column. First, eluted with 2.0 liters of 30% ethanol aqueous solution, collecting one portion every 500 ml, and collecting a total of 4 components (Fr.1~Fr.4), then eluted with 5.0 liters of 55% ethanol aqueous solution, collecting one portion every 500 ml, and collecting a total of 10 components (Fr.5~Fr.14). Each component was detected by HPLC, and the components containing ginsenosides Rg1, Re, Rb1, Rc, Rb2, Rb3 and Rd (Fr.4~Fr.12) were combined and concentrated under reduced pressure to complete dryness to obtain holographic ginsenoside components HGC1 (24.60 g, yield 82.0%), HGC2 (23.66 g, yield 78.9%), HGC3 (23.16, yield 77.2%), respectively. %), HGC4 (22.70, yield 75.7%), HGC5 (23.48, yield 78.3%), HGC6 (22.80, yield 76.0%), HGC7 (24.56, yield 81.9%), HGC8 (23.61, yield 78.7%), HGC9 (24.63, yield 82.1%), and HGC10 (22.9, yield 76.3%). The contents of the seven ginsenosides in these fractions were then determined by HPLC, and their relative proportions were analyzed.

[0256] Table 10 Content of each saponin in the holographic ginsenoside compositions (HGC1-HGC10) obtained by comprehensively utilizing total saponins from ginseng, American ginseng, and Panax notoginseng using ten different feeding schemes (%, n=3)

[0257] The research results are shown in Table 10. The 10 holographic ginsenoside compositions (HGC1~HGC10) prepared by 10 different feeding schemes all meet the following conditions: the total amount of ginsenosides and ginsenodiol saponins is greater than 80%, among which the total amount of ginsenosides is 1.8~4.4 times higher than the total amount of ginsenosides; the content of each of the five ginsenosides Re, Rb1, Rc, Rb3 and Rd is greater than 5% and less than 25%, but does not include the case where the content of these five ginsenosides is greater than 15% at the same time; the content of Rg1 is between 2.80~7.71%, and the content of Rb2 is between 4.72~10.45%.

[0258] Next, the efficacy of the above 10 ginsenoside compositions was investigated using the HAL-induced mouse stiffness model, which reflects the efficacy of the drug on motor symptoms (i.e., treating symptoms), and the rotenone (ROT)-induced rat PD model, which reflects the efficacy of the drug on preventing and treating the occurrence and development of PD (i.e., treating the root cause). As shown in Table 11, all 10 ginsenoside compositions, administered at a dose of 60 mg / kg, significantly antagonized the stiffness symptoms of HAL-induced mice ( ###p<0.001), and no significant difference was found in the efficacy of each combination.

[0259] Table 11 Effects of holographic ginsenoside compositions (HGC) obtained from ten different feeding schemes on HAL-induced stiffness in mice (mean ± SEM, n = 10) Note: One-way ANOVA was used to analyze the experimental data. Compared with the HAL group before HAL administration, *** p<0.001; compared with the HAL group after HAL administration, ### p<0.001.

[0260] However, in the ROT-induced PD rat model, significant differences in efficacy were observed among the 10 compositions at a dose of 60 mg / kg (Table 12). Among the 10 compositions, HGC6, HGC7, and HGC8 showed no significant protective efficacy, while the protective efficacy of the other seven effective compositions varied. Among them, HGC1, HGC2, HGC4, and HGC9 showed comparable efficacy, almost completely protecting against ROT-induced PD in rats. HGC3 and HGC5 were second best, followed by HGC10.

[0261] Results from studies in the HAL and ROT animal models demonstrate that HGC1 to HGC5, HGC9, and HGC10 are all effective combinations for treating both the symptoms and the root cause of PD, with HGC1, HGC2, HGC4, and HGC9 being particularly effective. Combined with the content and configuration of the individual ginsenoside components in each combination (Table 10), these efficacy results further suggest that arbitrary adducts of the active ginsenosides Rg1, Re, Rb1, Rc, Rb2, Rb3, and Rd are not effective in preventing and treating PD, and that the appropriate ratio of these active ginsenosides may be the key to determining efficacy. This possibility will be examined in subsequent studies.

[0262] Table 12 Effects of holographic ginsenoside compositions (HGC) obtained from ten different feeding schemes on the formation of PD in rats induced by ROT (mean ± SEM, n = 7) Note: One-way ANOVA was used to analyze the experimental data. *** p<0.001; compared with ROT group, # p<0.05, ## p<0.01, ### p<0.001.

[0263] The results of Example 4 are summarized as follows: For a long time, anti-PD drugs have been symptomatic treatments worldwide, and there is no drug that can prevent and treat the occurrence and development of PD. Moreover, dopamine drugs are ineffective for gait freezing and postural imbalance (easy to fall) in patients with middle and late PD. It can be seen that those holographic ginsenoside compositions (HGCs) that have significant efficacy on the HAL-induced stiffness model (simulating gait freezing and postural imbalance in patients with middle and late PD) and the ROT-induced PD occurrence and development model, including HGC1 to HGC5, HGC9 and HGC10 (especially HGC1, HGC2, HGC4 and HGC9), can play a role in treating both the symptoms and the root cause of PD and have great medicinal value for preventing and treating PD. Therefore, these compositions are referred to as superior compositions, and subsequent compositions that have significant efficacy on the above two PD animal models are collectively referred to as superior compositions. Therefore, the above-mentioned feeding schemes (1), (2), (3), (4), (5), (9) and (10) can all be used as preferred schemes for preparing the effective composition, among which (1), (2), (4) and (9) are the best of the best. Of course, in order to avoid the difference in the content of active ingredients caused by raw medicinal materials of different years, the preferred feeding scheme can be adjusted accordingly according to actual conditions.

[0264] In particular, the research results indicate that the optimal ratio of the different active ginsenosides in a composition is crucial for determining the strength of its therapeutic efficacy. Therefore, further understanding this optimal ratio is crucial for developing consistently effective and high-quality compositions. Consequently, the differences in the therapeutic efficacy of different holographic ginsenoside compositions can be used to analyze the relationship between efficacy and the compositional distribution of the major ginsenoside components within the composition, thereby revealing the patterns in the active ingredient distribution of effective compositions.

[0265] Example 5. Analysis of the relationship between the content and efficacy of each major ginsenoside component in the holographic ginsenoside composition (HGC).

[0266] Example 5-1. The content of ginsenoside Rb2 (Rb2) in HGC does not affect the anti-PD efficacy of HGC within a certain range.

[0267] As shown in Table 10, the total saponin content and total ginsenoside content of each composition were at the same level, eliminating the influence of these two factors on the efficacy of different holographic ginsenoside compositions. Therefore, the content configuration of the different effective individual components is crucial. Furthermore, the research data (Tables 10 and 12) suggest that the Rb2 content does not contribute significantly to the efficacy of the compositions against HAL-induced stiffness symptoms and ROT-induced PD formation, thus eliminating its role as a major active ingredient in the anti-PD efficacy.

[0268] Example 5-2. Analysis of the relationship between the content configuration of the main individual components in the holographic ginsenoside composition (HGC) and its efficacy.

[0269] Based on the above research results, the research data table of Example 4 (Table 13) was used to intuitively analyze the relationship between the relative content configuration of the two ginsenosides (Rg1 and Re) and the four ginsenosides (Rb1, Rc, Rb3, and Rd) and the efficacy of the composition. The content of Re in the composition is much higher than that of Rg1, and it is known that the biological activity and pharmacological effect strength of these two individual components are similar. Therefore, Re is the representative of the ginsenosides in the composition. Therefore, Re is used as a functional unit when analyzing the relationship between the content configuration of the main individual components in the composition and the efficacy. It is known that Rb1 is converted into Rd by the intestinal flora in the intestine. Therefore, Rb1 and Rd are classified as the same functional unit, while Rc and Rb3 are classified as another functional unit.

[0270] Accordingly, the applicant set the ratios of TPDS / TPTS (total ginsenosides of ginsenosides / total ginsenosides of ginsenosides), Re / Rg1, Rb1 / Re, Rb1 / Rd, Rb1 / Rc, Rb1 / Rb3, Rc / Rb3 and (Rb1+Rd) / (Rc+Rb3) (hereinafter referred to as 8 ratios) to reveal the relationship between the content configuration of the main individual components in the holographic ginsenoside composition (HGC) and the efficacy. The level of effectiveness is judged according to the statistical results of the experimental data, p>0.05, ineffective; p<0.05, effective (+); p<0.01, very effective (++); p<0.001, very very effective (+++). The efficacy intensity of the ROT model is based on the efficacy of the last ROT administration, that is, the last administration the day after the last administration.

[0271] As shown in Table 13, for each holographic ginsenoside composition (HGC1~HGC10) that is very effective against HAL-induced PD stiffness, the allowable ranges of the eight ratios are: TPDS / TPTS=1.88~4.40, Re / Rg1=2.31~4.41, Rb1 / Re=0.64~1.86, Rb1 / Rd=0.79~2.08, Rb1 / Rc=0.67~2.17, Rb1 / Rb3=0.82~2.76, Rc / Rb3=0.79~2.11, (Rb1+Rd) / (Rc+Rb3)=0.66~1.92. It is noteworthy that for each holographic ginsenoside composition (HGC1-HGC5, HGC9, and HGC10) that is highly effective against ROT-induced PD in rats, except for the Rc / Rb3 ratio, the ranges of the other seven ratios have narrowed to: TPDS / TPTS = 1.88-4.29, Re / Rg1 = 2.33-4.03, Rb1 / Re = 0.64-1.53, Rb1 / Rd = 0.79-1.56, Rb1 / Rc = 0.75-2.17, Rb1 / Rb3 = 0.93-2.20, and (Rb1+Rd) / (Rc+Rb3) = 0.76-1.92. Therefore, these eight ratio ranges with excellent efficacy against the ROT model can be used as quality standards for the preparation of highly effective holographic ginsenoside compositions (HGC). HGC1 to HGC5, HGC9, and HGC10 meet this quality standard, and their Rg1 / Re / Rb1 / Rc / Rb3 / Rd ratios are 0.60 / 2.13 / 2.17 / 1.00 / 1.27 / 2.12, 0.76 / 2.16 / 1.38 / 1.00 / 0.63 / 1.74, and 0.37 / 0.86 / 1.00 / 1. 0.00 / 0.47 / 0.64, 0.28 / 0.66 / 0.76 / 1.00 / 0.68 / 0.52, 0.39 / 0.91 / 0.75 / 1.00 / 0.56 / 0.66, 0.23 / 0.91 / 1.39 / 1.00 / 1.09 / 0.91, and 0.21 / 0.76 / 1.01 / 1.00 / 1.09 / 0.73. It can be seen that there is no regular change in the relative ratios of the six ginsenoside active ingredients in these effective compositions. Moreover, these ratio ranges do not show any regional differences from the Rg1 / Re / Rb1 / Rc / Rb3 / Rd ratio ranges of the compositions with poor efficacy in the ROT model (HGC6-HGC8). Therefore, the quality standard of the superior composition cannot be formulated solely by the relative values ​​of the contents of these six ginsenoside components, but the eight ratios are required as the quality standard.

[0272] Table 13 Effects of the content of main individual ginsenosides in holographic ginsenoside compositions on their efficacy Note: TPDS: total content of ginsenosides; TPTS: total content of ginsenosides. The effectiveness level was determined based on the statistical results of the research data in Example 4: p>0.05, ineffective; p<0.05, effective (+); p<0.01, very effective (++); p<0.001, very very effective (+++).

[0273] in conclusion

[0274] The above parameters further clearly demonstrate the unpredictability of the 8 ratio in the superior efficacy composition, and each superior efficacy composition has its own 8 ratio, which further highlights the unconventionality of the present invention and its significant use value. Furthermore, under certain content ratio conditions, different active ginsenosides cannot synergize with each other to produce significant pharmacological effects or even weaken each other's respective pharmacological effects, so that the mixture of multiple single active ginsenosides has no pharmacological guarantee. Similarly, the pharmacological effect of the superior efficacy composition is not the sum of the independent pharmacological effects of the effective single ingredients, but the result of the synergistic effect of the combination of different single ingredients, and a reasonable 8 ratio is the essence of the superior efficacy combination. Obviously, these findings have broken the conventional understanding of professional and technical personnel in this field on the use of ginsenoside biological activity and pharmacological effects, which is conducive to avoiding ineffective and inefficient use of ginsenosides. More importantly, these findings reveal that the biological activity and pharmacological effects of ginsenosides can be enhanced and expanded through the combined use of active ginsenoside ingredients, which has great potential for serving the health care and disease treatment of Panax genus medicinal materials (ginseng, American ginseng and Panax notoginseng) and the ginsenosides they contain. Therefore, the superior combination including HGC1 to HGC5, HGC9 and HGC10 is not only an excellent combination for the prevention and treatment of PD, but can also be applied to the nervous system, cardiovascular system, immune system and endocrine system and its systemic sub-health conditions.

[0275] Example 6. The ginsenoside composition contained in the superior holographic ginsenoside composition has the effect of treating both the symptoms and the root cause of PD.

[0276] In order to further explore the compatibility rules of the main active ginsenoside components that may be present in the high-efficiency holographic ginsenoside composition, the applicant chose to study the optimal compatibility or compatibility rules of the four main active ginsenosides (Rb1, Rc, Rb3 and Rd). To this end, first, the same feeding scheme used to prepare the holographic ginsenoside composition (HGC) was selected to prepare the corresponding ginsenoside composition (PDSC) rich only in ginsenosides; then, the efficacy of these ginsenoside compositions (PDSC) in treating PD was evaluated using the two animal models used previously, one for treating symptoms and the other for treating the root cause.

[0277] Example 6-1. Preparation of a ginsenoside composition (PDSC) corresponding to a holographic ginsenoside composition (HGC).

[0278] More specifically, (1) PDSC1 was prepared from a mixture of "1 part of total saponins from American ginseng roots + 2 parts of total saponins from American ginseng stems and leaves", (2) PDSC2 was prepared from a mixture of "1 part of total saponins from ginseng roots + 1 part of total saponins from American ginseng roots + 1 part of total saponins from ginseng stems and leaves + 3 parts of total saponins from American ginseng stems and leaves", (3) PDSC4 was prepared from a mixture of "2 parts of total saponins from ginseng roots + 1 part of total saponins from ginseng stems and leaves + 2 parts of total saponins from Panax notoginseng stems and leaves", and (4) PDSC5 was prepared from a mixture of "1 part of total saponins from ginseng roots + 1 part of total saponins from ginseng stems and leaves + 1 part of total saponins from Panax notoginseng stems and leaves". , (5) PDSC6 was prepared from the mixture of "1 part of total saponins from ginseng roots + 1 part of total saponins from ginseng stems and leaves + 2 parts of total saponins from Panax notoginseng stems and leaves", (6) PDSC7 was prepared from the mixture of "2 parts of total saponins from American ginseng roots + 1 part of total saponins from American ginseng stems and leaves + 1 part of total saponins from Panax notoginseng stems and leaves", (7) PDSC9 was prepared from the mixture of "1 part of total saponins from American ginseng roots + 1 part of total saponins from American ginseng stems and leaves + 1 part of total saponins from Panax notoginseng stems and leaves", (8) PDSC10 was prepared from the mixture of "1 part of total saponins from American ginseng roots + 1 part of total saponins from American ginseng stems and leaves + 2 parts of total saponins from Panax notoginseng stems and leaves". Among them, the holographic ginsenoside compositions HGC1, HGC2, HGC4, HGC5, HGC9 and HGC10 prepared by the feeding schemes (1), (2), (4), (5), (9) and (10) are superior compositions, while the holographic ginsenoside compositions HGC6 and HGC7 prepared by the feeding schemes (6) and (7) have poor efficacy.

[0279] The specific preparation method is as follows: 30 g of each mixture described in the feeding scheme is dissolved in 300 ml of 30% ethanol aqueous solution, and the mixture is loaded on a reverse phase C 18A silica gel (ODS, 300 g) chromatography column was first eluted with 2.0 L of 30% ethanol in water, the 30% ethanol eluate discarded, and then eluted with 3.0 L of 43% ethanol in water, collecting 500 mL portions of the eluate for a total of 6 fractions (Fr. 1 to Fr. 6). Then, eluted with 6.0 L of 55% ethanol in water, collecting 500 mL portions for a total of 10 fractions (Fr. 7 to Fr. 18). The components were detected by HPLC, and the components (Fr.7 to Fr.15) containing ginsenosides Rb1, Rc, Rb2, Rb3 and Rd were combined and concentrated under reduced pressure to complete dryness to obtain ginsenoside compositions PDSC1 (15.16 g, yield 50.5%), PDSC2 (13.88 g, yield 46.3%), PDSC4 (16.77, yield 55.9%), PDSC5 (15.09, yield 50.3%), PDSC6 (16.12, yield 53.7%), PDSC7 (16.41, yield 54.7%), PDSC9 (17.01, yield 56.7%) and PDSC10 (16.68, yield 55.6%), respectively.

[0280] Table 14 Content of each saponin and total content in the ginsenoside composition (PDSC) corresponding to the holographic ginsenoside composition (HGC) (%, n=3)

[0281] Table 15 Content configuration of each main component in the ginsenoside composition (PDSC) corresponding to the holographic ginsenoside composition (HGC)

[0282] The contents of the five ginsenoside components, Rb1, Rc, Rb2, Rb3, and Rd, and their total content in the ginsenoside composition (PDSC) were determined using a conventional HPLC method, and the ratios of Rb1 / Rd, Rb1 / Rc, Rb1 / Rb3, Rc / Rb3, and (Rb1+Rd) / (Rc+Rb3) were calculated. The analytical data showed that the total amount of the five ginsenoside components, Rb1, Rc, Rb2, Rb3, and Rd, in the eight compositions accounted for more than 91% of the composition (Table 14). The Rb1 / Rd, Rb1 / Rc, Rb1 / Rb3, Rc / Rb3, and (Rb1+Rd) / (Rc+Rb3) ratios in each composition (Table 15) were consistent with those in the corresponding holographic ginsenoside composition (HGC) (Table 13).

[0283] Example 6-2. Determination of the efficacy of the ginsenoside composition (PDSC) corresponding to the holographic ginsenoside composition (HGC) in treating the symptoms and the root cause of PD.

[0284] The HAL-induced stiffness model in mice was used to determine the efficacy of PDSC1, PDSC2, PDSC4, PDSC5, PDFSF6, PDSC7, PDSC9, and PDSC10 against motor symptoms of PD caused by dopamine signaling deficiency. The efficacy of the anticholinergic drug Antan, which is used to alleviate motor symptoms, was also compared and observed.

[0285] Table 16 Effect of PDSCs corresponding to HGC on HAL-induced stiffness in mice (mean ± SEM, n = 10) Note: One-way ANOVA was used to analyze the experimental data. Compared with the HAL group before HAL administration, ** p<0.01, *** p <0.001; compared with the HAL group after HAL administration, ### p<0.001; compared with PDSC1 group, & p<0.05.

[0286] The research data (Table 16) show that these compositions can all significantly counteract the stiffness symptoms induced by HAL in mice, but the efficacy of different compositions varies. Among them, PDSC1, PDSC2, and PDSC7 are the most effective and are all stronger than Antan. There is no significant difference in the efficacy of the compositions, and their efficacy (Table 16) is consistent with the efficacy of their corresponding holographic ginsenoside compositions (HGC) (Table 11). However, PDSC2 is the exception, and its efficacy is superior to PDSC4, PDSC5, PDSC9, and PDSC910, while HGC2 has the opposite efficacy relative to them. This indicates that the ginsenoside composition (PTSC) in HGC2 may weaken the efficacy of the ginsenoside composition (PDSC). Notably, the PDSC-to-PTSC ratio in HGC3 is 3.06 (Table 13). While HGCs composed of a mixture of PTSC1 and PDSC1 at this exact ratio were less effective than PDSC1, the addition of PTSC1 at ratios greater than or less than this did not significantly diminish PDSC1's efficacy (Table 6). This further suggests that HGCs containing 1 / 4 PTSCs are not conducive to alleviating motor symptoms caused by insufficient dopamine signaling or hyperactive acetylcholine signaling.

[0287] In summary, we can draw the following conclusions:

[0288] (1) Panaxadiol saponin composition (PDSC) is the main active ingredient of the holographic ginsenoside composition (HGC) in combating stiffness symptoms in HAL-induced mice and can be used as an ideal medicinal form for controlling motor symptoms of PD.

[0289] (2) The efficacy of PDSCs obtained from different feed ratios of the same medicinal materials was different, indicating that the content configuration of the main ginsenoside components was related to the efficacy of PDSCs in alleviating PD motor symptoms. The relationship between the two will be revealed in subsequent studies.

[0290] (3) In most cases, HGC and the corresponding PDSC have comparable efficacy in alleviating PD motor symptoms, which again indicates that HGC is also an effective medication form for alleviating PD motor symptoms. In addition, using HGC as a medicinal form can save 1 / 3 to 1 / 5 of the ginsenoside resources.

[0291] (4) Since hyperactivity of acetylcholine signaling is the neurochemical essence of HAL-induced rigidity, the weakening of PDSC's effect against HAL-induced rigidity by PTSC reflects its pharmacological effect of promoting acetylcholine signaling. Insufficient acetylcholine signaling associated with neurodegeneration is closely related to cognitive impairment in late-stage PD patients and is also involved in cognitive impairment in Alzheimer's disease. This predicts that HGC is more suitable for late-stage PD patients and AD patients than PDSC and those PDSCs with weaker efficacy against HAL-induced rigidity, such as PDSC5 and PDSC10. The corresponding total ginsenoside composition is also more suitable for improving memory loss in normal elderly people.

[0292] It should also be noted that the efficacy of the ginsenoside composition against haloperidol (an antipsychotic)-induced rigidity in mice also supports the medical use of the ginsenoside composition for preventing and treating drug-induced Parkinson's disease-like symptoms (DIP). DIP, also known as drug-induced parkinsonism, is the second most common cause of Parkinson's disease after PD. Drug-induced DIP, secondary to antipsychotics and other dopamine antagonists, is very common in clinical practice and is insensitive to dopamine drugs. Currently, DIP is alleviated clinically by discontinuing the drug or using anticholinergics with severe side effects. Therefore, the holographic ginsenoside composition (HGC), particularly the ginsenoside compositions PDSC1 and PDSC2, will provide a new approach to preventing and treating DIP that is safer and more effective than Antan.

[0293] The efficacy of the superior HGCs and their corresponding PDSCs, including HGC1, PDSC1, HGC2, PDSC2, HGC4, PDSC4, HGC9, and PDSC9, was further evaluated in a ROT-induced PD rat model. Furthermore, the efficacy of two ginsenoside compositions, PDSC6 and PDSC7, corresponding to HGC6 and HGC7 (not the superior composition), was compared. The dose of each composition was 40 mg / kg, and the methods used were the same as above.

[0294] The experimental results are shown in Table 17. Except for PDSC6 and PDSC7, the other ginsenoside compositions can significantly counteract the formation of PD model in rats induced by ROT, and there is no significant difference between the compositions. It is manifested that all the indicators measured at two time points, namely the day after the last dose of the test drug and the third day after the drug withdrawal, namely the 2-day drug withdrawal, are significantly better than the ROT control group, and close to the normal control. In particular, these superior PDSCs and their corresponding holographic ginsenoside compositions (HGC) exhibit the same efficacy (Table 12). Consistent with HGC6 and HGC7, PDSC6 and PDSC7 can only partially improve the motor behavior and premise lifting ability on the rotating rod. The results of the study show that PDSC is an indispensable active ingredient of HGC against the formation of ROT-induced PD rat model, and the content configuration of Rb1, Rc, Rb3 and Rd is the key factor in determining whether HGC and PDSC can counteract the occurrence and development of PD induced by mitochondrial complex enzyme I deficiency and its efficacy.

[0295] Table 17 Effects of HGC and corresponding PDSC on ROT-induced PD formation in rats (mean ± SEM, n = 5) Note: One-way ANOVA was used to analyze the experimental data. *** p<0.001; compared with ROT group, ### p<0.001; compared with PDSC1 group, & p<0.05, && p<0.01.

[0296] Example 6-3. Analysis of the relationship between the content configuration and pharmacodynamics of ginsenosides Rb1, Rc, Rb3 and Rd.

[0297] Here, using the research data from Examples 6-1 and 6-2, we further tabulate and visually analyze the relationship between the content configuration of Rb1, Rc, Rb3, and Rd and their efficacy. This research result provides a quality standard for the preparation of high-performance compositions with stable and controllable quality. As shown in Table 18, the purity of ginsenosides from different HGCs and their corresponding PDSCs varies between 4 and 10%. However, this difference is not associated with the poor efficacy of HGC6, PDSC6, HGC7, and PDSC7 in the ROT model. The relative content of the various ginsenosides is closely related to their efficacy. Specifically, the Rb1 / Rd ratio of the superior composition (which had very significant efficacy in both the HAL and ROT models) was between 0.79 and 1.53, the Rb1 / Rc ratio was between 0.76 and 2.17, the Rb1 / Rb3 ratio was between 1.11 and 2.20, the Rc / Rb3 ratio was between 0.79 and 1.59, and the (Rb1+Rd) / (Rc+Rb3) ratio was between 0.76 and 1.92, all falling within the superior efficacy range. These analysis results are completely consistent with the analysis results in Table 13 (Effect of the Content Configuration of the Main Individual Ginsenosides in the Holographic Ginsenoside Composition on Efficacy), and combined with Table 13 and Table 18, it can be further confirmed that the superior efficacy range of the Rc / Rb3 ratio is between 0.79 and 1.59.

[0298] Based on the research results of Examples 3 to 6, the following three conclusions can be obtained:

[0299] (1) Panaxadiol saponins are the essential active ingredients of holographic ginsenoside composition (HGC) and panaxadiol saponin composition (PDSC) for treating both the root cause and symptoms of PD.

[0300] (2) At the same dose, the efficacy of the superior HGC is comparable to that of its corresponding PDSC for both symptomatic and fundamental treatment. That is, according to the HPLC test results (Table 10), PDSC at a dose of 2 / 3 to 4 / 5 of the holographic ginsenoside composition (HGC) can exert its full-dose efficacy, indicating that both superior HGC and superior PDSC are ideal medicinal forms. Using the holographic ginsenoside composition (HGC) as a medicinal form can reduce the dosage of the ginsenoside composition (PDSC) by 1 / 3 to 1 / 5, which is of great value in alleviating the shortage of ginseng, American ginseng, and Panax notoginseng medicinal resources, thereby further supporting the view that the holographic ginsenoside composition (HGC) is an economical, efficient, and scientific medicinal form. In particular, from the perspective of medicinal properties, the ability of the superior ginsenoside composition (PDSC) to correct central hyperexcitability is stronger than that of the holographic ginsenoside composition (HGC). Therefore, it can be expected that PDSC can better serve patients with prominent hyperexcitability than HGC. In theory, these patients should have prominent PD motor symptoms. The active ingredient Re can give HGC a broader brain protective effect, so in terms of the efficacy of atypical Parkinson's syndrome, HGC may be better than PDSC. Therefore, HGC or PDSC can be used flexibly according to the specific circumstances of the disease and the patient, but this needs to be verified by clinical trials.

[0301] (3) The content of Rb1, Rc, Rb3, and Rd is a key factor in determining whether HGC and PDSC can resist the occurrence and development of PD induced by mitochondrial complex I deficiency and the intensity of their efficacy. The ratios of the four ginsenosides in the effective combination (which has very significant efficacy in both HAL and ROT PD models) have the following characteristics: Rb1 / Rd ratio is between 0.79 and 1.53, Rb1 / Rc ratio is between 0.76 and 2.17, Rb1 / Rb3 ratio is between 1.11 and 2.20, Rc / Rb3 ratio is between 0.79 and 1.59, and (Rb1+Rd) / (Rc+Rb3) ratio is between 0.76 and 1.92.

[0302] Table 18 Effects of the content of the main ginsenoside components in HGC and its corresponding PDSC on the efficacy Note: The effectiveness level is determined based on the statistical results of the research data in Example 6: p>0.05, ineffective; p<0.05, effective / +; p<0.01, very effective / ++; p<0.001, very very effective / +++.

[0303] Example 7. Effects of the Rc / Rb3 ratio and the (Rb1+Rd) / (Rc+Rb3) ratio on the efficacy of PDSCs.

[0304] Based on the above-mentioned optimal efficacy range, the applicant attempted to further explore possible optimal 5-ratio values. To this end, using PDSC1 as an example, the applicant added high-purity Rc and Rb3 to the optimal PDSC1 to gradually change the 5-ratio. The applicant then observed the efficacy changes of these new compositions using the HAL-induced mouse stiffness model and the ROT-induced rat PD development model.

[0305] Example 7-1. PDSC1-1 to PDSC1-8 were prepared by adding different amounts of Rc and Rb3 to PDSC1.

[0306] First, a high-purity mixture of Rc and Rb3 was isolated from the total saponins in Panax notoginseng stems and leaves using conventional methods. This mixture was then added to PDSC1 to gradually increase the Rc and Rb3 content, yielding PDSC1 derivatives PDSC1-1 to PDSC1-8. The content of each panaxadiol saponin and the total saponin content in these compositions were determined using HPLC analysis, and their ratios were calculated. The experimental results (Tables 19 and 20) show that the total saponin content of these compositions is above 92.8%, and their Rb1 / Rd ratio gradually increases from 1.03 of PDSC1 to 1.75, while the Rb1 / Rc, Rc / Rb3 and (Rb1+Rd) / (Rc+Rb3) ratios gradually decrease from 2.17, 1.71 and 1.89 of PDSC1 to 0.91, 0.70 and 0.62, respectively, while their Rc / Rb3 ratio does not change much (between 0.76 and 0.88).

[0307] Table 19 Contents of individual ginsenosides and total saponins in PDSC1 and its derived PDSC compositions (%, n=3)

[0308] Table 20 Content of each ginsenoside active ingredient in PDSC1 and its derived PDSC composition

[0309] Example 7-2. Effect of PDSCl derivative compositions with higher Rc and Rb3 ratios on the efficacy of PD treatment.

[0310] First, the HAL-induced mouse stiffness model was used to compare the efficacy of PDSC1 and its derivatives in alleviating PD motor symptoms. Then, based on actual conditions, a comparative study was conducted on the efficacy of PDSC1 and its derivatives in combating ROT-induced PD in rats.

[0311] As shown in Table 21, all six compositions, PDSC1-1 through PDSC1-6, significantly combated HAL-induced stiffness in mice, with comparable potency to PDSC1. This suggests that significantly altering the Rb1 / Rd, Rb1 / Rc, Rc / Rb3, and (Rb1+Rd) / (Rc+Rb3) ratios in PDSC1 did not affect its efficacy against motor symptoms of PD caused by insufficient dopamine signaling. Furthermore, these results suggest the importance of Rc and Rb3, as well as the Rc / Rb3 ratio, for the effectiveness of the most effective compositions against HAL-induced stiffness.

[0312] Table 21: Efficacy of PDSC1 derivative compositions that increase the ratio of Rc to Rb3 against HAL-induced stiffness in mice (mean ± SEM, n = 10) Note: One-way ANOVA was used to analyze the experimental data. Compared with the HAL group before HAL administration, *** p<0.001; compared with the HAL group after HAL administration, ### p<0.001.

[0313] However, as shown in Table 22, the four compositions, PDSC1-1 to PDSC1-4, showed varying degrees of efficacy against ROT-induced PD formation in rats, and none of them were as effective as the parent PDSC1. The efficacy of PDSC1-1 and PDSC1-3 was even weaker, far less than that of PDSC1. The results suggest that, for PDSC1, while maintaining a substantially unchanged Rc / Rb3 ratio, simultaneously increasing the Rb1 / Rd ratio and decreasing the Rb1 / Rc, Rc / Rb3, and (Rb1+Rd) / (Rc+Rb3) ratios is not conducive to its efficacy against ROT-induced PD formation in rats.

[0314] Table 22 Effect of increasing the ratio of Rc to Rb3 on the efficacy of PDSC1 against rotenone (ROT)-induced PD in rats (mean ± SEM, n = 7) Note: One-way ANOVA was used to analyze the experimental data. *** p<0.001; compared with ROT group, # p<0.05, ## p<0.01, ### p<0.001.

[0315] However, the four ratio ranges of the superior compositions (which have very significant efficacy in both HAL and ROT models) shown in Table 18 are Rb1 / Rd between 0.79 and 1.53, Rb1 / Rc between 0.76 and 2.17, Rb1 / Rb3 between 1.11 and 2.20, and (Rb1+Rd) / (Rc+Rb3) between 0.76 and 1.92), while the three ratios Rb1 / Rc, Rb1 / Rb3 and (Rb1+Rd) / (Rc+Rb3) in the four compositions PDSC1-1 to PDSC1-4 are all within the superior efficacy range, and the Rb1 / Rd ratio (1.52 to 1.66) is also very close to its superior efficacy range (Table 20). Therefore, this indicates that PDSC1 and other superior PDSCs and HGCs have their own specific Rb1 / Rd, Rb1 / Rc, Rb1 / Rb3 and (Rb1+Rd) / (Rc+Rb3) ratios.

[0316] Example 7-3. Effect of significantly increasing the Rc / Rb3 ratio on the efficacy of the superior composition in treating PD.

[0317] To further explore whether each superior composition has its own specific Rc / Rb3 ratio, based on the known superior composition Rc / Rb3 ratio range of 0.79 to 2.11 (Table 13), the applicant took the superior composition PDSC9 as an example, and while keeping the other four ratios basically unchanged, changed the Rc / Rb3 ratio within the superior range, and used the above two animal models to determine the effect of this change on efficacy. To this end, using the superior composition PDSC9 as a reference, the PDSC9-1 composition was constructed using a single component, increasing its Rc / Rb3 ratio from the original 0.92 to 1.68, while keeping the other ratios basically unchanged or with little change (Table 23).

[0318] Table 23 Panaxadiol saponin content in PDSC9 and its derivative PDSC9-1

[0319] The efficacy of PDSC9 and PDSC9-1 was determined using the same method as described above. As shown in Table 24, PDSC9-1 could significantly counteract the stiffness symptoms induced by HAL in mice, but its efficacy showed a weakening trend compared with PDSC9.

[0320] Table 24 Effect of increasing the Rc / Rb3 ratio on the efficacy of PDSC9 against HAL-induced stiffness in mice (mean ± SEM, n = 10) Note: One-way ANOVA was used to analyze the experimental data. Compared with the HAL group before HAL administration, *** p<0.001; compared with the HAL group after HAL administration, ### p<0.001.

[0321] However, the potency of PDSC9-1 against ROT-induced PD formation in rats was significantly weaker than that of PDSC9 (Table 25). Thus, among the five ratios in PDSC9, only increasing the Rc / Rb3 ratio (from 0.92 to 1.68) significantly reduced the potency. In contrast, Table 13 shows that the Rc / Rb3 ratios of the most potent compositions ranged from 0.79 to 1.77. Therefore, the results suggest that PDSC9 and other potent PDSCs and HGCs also have specific Rc / Rb3 ratios.

[0322] Summary and discussion of the research results of Examples 3 to 7:

[0323] The results of Examples 3 to 7 above indicate that the highly effective panaxadiol saponin compositions (PDSC) and the highly effective holographic ginsenoside compositions (HGC) each represent a specific, highly effective combination (Tables 13 and 15). In other words, each PDSC and HGC is an independent organism. Furthermore, the five ratios of Rb1 / Rd, Rb1 / Rc, Rb1 / Rb3, Rc / RRb3, and (Rb1+Rd) / (Rc+Rb3) collectively constitute the essence of the HGC-PDSC combination. Specifically, the 5 ratios of HGC1 and PDSC1 were 1.03, 2.17, 1.71, 0.79, and 1.89, respectively; the 5 ratios of HGC2 and PDSC2 were 0.79, 1.38, 2.20, 1.59, and 1.92, respectively; the 5 ratios of HGC3 and PDSC3 were 1.56, 1.00, 2.11, 2.11, and 1.11, respectively; the 5 ratios of HGC4 and PDSC4 were 1.45, 0.76, 1.11, 1.46, and 0.76, respectively; and the 5 ratios of HGC5 and PDSC5 were 1.13, 0.75, 1.32, 1.77, and 1.91, respectively. The 5 ratios of HGC9 and PDSC9 are 1.53, 1.39, 1.28, 0.92 and 1.10, respectively, and the 5 ratios of HGC10 and PDSC10 are 1.39, 1.01, 0.93, 0.92 and 0.83, respectively. Moreover, these 5 ratios have their own upper and lower limits, which are 1.56 and 0.79 (Rb1 / Rd), 2.17 and 0.75 (Rb1 / Rc), 2.20 and 0.93 (Rb1 / Rb3), 2.11 and 0.79 (Rc / Rb3), and 1.92 and 0.76 (Rb1+Rd) / (Rc+Rb3), respectively. However, the TPDS / TPTS, Re / Rg1, and Rb1 / Re ratios in these HGCs can vary within a certain range, ranging from 1.88 to 4.29, 2.33 to 4.03, and 0.64 to 1.53, respectively, and it is not ruled out that these ratios may extend to larger or smaller values. These ratio parameters provide a basis for formulating feed ratios and product quality standards for the comprehensive utilization of Panax genus medicinal materials to prepare active or potent holographic ginsenoside compositions (HGCs) and active and potent ginsenoside compositions (PDSCs), and also lay a solid foundation for subsequent research on the intrinsic relationship between the composition of effective ingredient combinations and efficacy.

[0324] Table 25 Effect of increasing the Rc / Rb3 ratio on the efficacy of PDSC9 against rotenone (ROT)-induced PD formation in rats (mean ± SEM) Note: One-way ANOVA was used to analyze the experimental data. *** p<0.001; compared with ROT group, # p<0.05, ##p<0.01, ### p<0.001; compared with PDSC9 group, & p<0.05.

[0325] Obviously, the discovery of these independent organisms (PDSC and HGC) is not an obvious result of reasoning, but a scientific discovery that goes against conventional thinking and has significant application and theoretical value. These unconventional discoveries not only provide a method for the comprehensive and flexible use of Panax genus medicinal materials to prepare a highly effective holographic ginsenoside composition (HGC) and a highly effective ginsenoside composition (PDSC) that has both symptomatic and root-treatment effects on PD, but also provide a scientific basis for the formulation of product quality standards. They also break the existing understanding of the medicinal value, economic value, and usage of ginseng, American ginseng, Panax notoginseng, and their stems and leaves. These discoveries not only reveal the significant application value of Panax genus medicinal materials and ginsenosides in preventing and treating Parkinson's disease and other neurodegenerative diseases, but also effectively alleviate the shortage of ginseng and American ginseng resources. By using roots, stems, and leaves in combination, the consumption of precious root medicinal materials is saved while the medicinal value of the inexpensive stems and leaves is maximized, thereby greatly reducing the preparation cost of the highly effective composition and greatly broadening the raw material resources for the promotion and application of subsequent products. In particular, the combination of roots, stems, and leaves, resulting in a potent holographic ginsenoside composition (HGC) and a potent panaxadiol saponin composition (PDSC), demonstrates efficacy not achieved by ginsenoside compositions or mixtures derived from roots or stems alone. In other words, HGC and PDSC's combined efficacy in treating both the root and root causes of PD surpasses the traditional medicinal value of ginseng, American ginseng, and Panax notoginseng. More importantly, HGC and PDSC will effectively address the long-standing stalemate in the lack of a drug that addresses both the root and root causes of PD, both domestically and internationally.

[0326] It is also worth noting that the research results also demonstrate that each highly effective composition incorporates complex and synergistic interactions or a well-balanced division of labor between Rb1, Rd, Rc, and Rb3, resulting in synergistic and even novel pharmacological effects and efficacy, thereby achieving a comprehensive treatment of both the symptoms and the root cause of PD. Clearly, further unraveling this complex and synergistic or cooperative relationship will not only deepen our understanding of the pharmacological implications of the compatibility between the active ingredients in HGC and PDSC, but will also be crucial for further exploring the medicinal value of ginsenosides. Accordingly, the applicant conducted research in Example 8.

[0327] Example 8. The contribution of different functional units in the superior composition to the efficacy of the superior composition in treating both the root cause and the symptoms of PD is studied to reveal the complex interactions or appropriate division of labor and cooperation between potential different active ingredients.

[0328] According to the two functional units in the above-mentioned superior composition, taking PDSC1 as an example, a decomposition study was conducted on the efficacy of the superior composition in treating both the symptoms and the root cause of PD to verify that there is a division of labor and cooperation relationship between the two functional units.

[0329] Example 8-1. Effects of functional units (Rb1+Rd) and (Rc+Rb3) on PDSC1's improvement of HAL-induced stiffness symptoms.

[0330] Research Methods: The experimental groups and dosage design are shown in Table 26. Based on the optimal dose of 60 mg / kg of PDSC1, two dosage groups of the functional units (Rb1+Rd) and (Rc+Rb3) were designed: ① both at 60 mg / kg (hereinafter referred to as the full dose), which can clarify whether the two functional units have the same effect as the full combination; ② the absolute doses of each in 60 mg / kg PDSC1 (hereinafter referred to as the constituent dose), namely 36 mg / kg (Rb1+Rd) and 24 mg / kg (Rc+Rb3), which can clarify the relative contribution of the two functional units in treating symptoms.

[0331] Table 26 Effects of the split composition of PDSC1 on HAL-induced stiffness in mice (mean ± SEM, n = 10) Note: One-way ANOVA was used to analyze the experimental data. Compared with the HAL group before HAL administration, *** p<0.001; compared with the HAL group after HAL administration, # p<0.05, ## p<0.01, ### p<0.001; compared with PDSC1 group, + p<0.05, ++ p<0.01,+++p<0.001.

[0332] Results: As shown in Table 26, at 60 mg / kg, the split composition (Rb1+Rd) significantly shortened two indicators reflecting stiffness, but the effect was less potent than the full composition PDSC1, while the functional unit (Rc+Rb3) failed to improve stiffness symptoms. Interestingly, at the actual composition dose of PDSC1, (Rb1+Rd) (36 mg / kg) actually aggravated HAL-induced stiffness symptoms, and (Rc+Rb3) (24 mg / kg) failed to improve HAL-induced stiffness symptoms. However, when the two were combined (+) to reconstruct the composition of PDSC1, the protective efficacy of PDSC1 was fully reproduced. It can be seen that neither the split parts (Rb1+Rd) nor (Rc+Rb3) can replace the full composition PDSC1. The effect of (Rb1+Rd) on improving stiffness symptoms is better than that of (Rc+Rb3), but its effective dose range is narrow, and the dose-effect relationship shows a jump-like two-way change. Although (Rc+Rb3) is not sufficient to improve stiffness symptoms, it can synergize with (Rb1+Rd) to exert positive pharmacological effects, while restraining the side effects of (Rb1+Rd), thereby making the overall efficacy of the formula significant, stable and reliable.

[0333] The research results validate the applicant's division of these two functional units in terms of efficacy and reveal their optimal collaboration in relieving stiffness. Specifically, the results demonstrate that the efficacy of the formula in relieving stiffness is the result of both quantitative and qualitative changes generated by this optimal collaboration between these two functional units.

[0334] Example 8-2. Exploring the dose-effect relationship of the functional unit (Rb1+Rd).

[0335] The unusual dose-effect relationship observed for the functional unit (Rb1+Rd) in Example 8-1: While significantly effective at 60 mg / kg, at 36 mg / kg, it was ineffective and significantly exacerbated HAL-induced stiffness in mice. This dose-effect relationship is inconsistent with conventional understanding of the dose-effect relationship of traditional Chinese medicine (TCM), which often exhibits an inverted U-shaped pattern: increasing efficacy with increasing dose within a certain range, followed by a plateau and a subsequent decline in efficacy. Therefore, we sought to further confirm this seemingly contradictory result and investigate whether a low dose of (Rb1+Rd) exacerbated stiffness. We then lowered the dose to 24 mg / kg, the absolute amount of (Rb1+Rd) present in 40 mg / kg of PDSC1.

[0336] Table 27 Effect of dose on the effect of functional unit (Rb1+Rd) on HAL-induced stiffness in mice (mean ± SEM, n = 10) Note: One-way ANOVA was used to analyze the experimental data. Compared with the HAL group before HAL administration, *** p<0.001; compared with the HAL group after HAL administration, ## p<0.01, ### p<0.001.

[0337] As shown in Table 27, (Rb1+Rd) repeated the test results of Example 8-1 at doses of 60 mg / kg and 36 mg / kg. However, unexpectedly, the 24 mg / kg dose of (Rb1+Rd) can significantly shorten the head turning time (Tturn) and the total pole climbing time (Ttotal), and its mathematical mean value shows that the efficacy of this dose tends to exceed that of the high-dose group. It can be seen that the dose-effect relationship of (Rb1+Rd) shows a non-inertial jump-like change in which high doses relieve stiffness, medium doses aggravate stiffness, and low doses are effective. The research results not only confirmed the findings of Example 8-1, that is, the dosage range of (Rb1+Rd) to relieve stiffness symptoms is narrow, and the dose-effect relationship shows a jump-like two-way change, and further found that this jump-like double change can occur at both ends of the dose that produces side effects.

[0338] Example 8-3. Study on the contribution of individual Rb1 and Rd to the alleviation of HAL-induced stiffness by PDSC1.

[0339] After clarifying the contribution of the functional unit (Rb1+Rd) to the full composition PDSC1 in alleviating stiffness symptoms, (Rb1+Rd) was separated into individual components to clarify the contribution of Rb1 and Rd to the efficacy of the functional unit (Rb1+Rd). The experimental results are shown in Table 28. At a dose of 60 mg / kg, both individual Rb1 and Rd showed partial efficacy, but the efficacy was not as comprehensive as that of the functional unit (Rb1+Rd). This was mainly manifested in the following ways: on the turning time at the top of the pole (Tturn), the efficacy of Rb1 and the functional unit (Rb1+Rd) was similar, while Rd had no significant efficacy. Conversely, on the total climbing time (Ttotal), the efficacy of Rd was close to that of the functional unit (Rb1+Rd), while Rb1 had no significant efficacy. The research results fully demonstrate that Rb1 and Rd are both active ingredients of the functional unit (Rb1+Rd) to relieve stiffness symptoms. The two cannot replace each other and must be used together.

[0340] Table 28 Contribution of individual Rb1 and Rd to the functional unit (Rb1+GRb) in alleviating HAL-induced stiffness in mice (mean ± SEM, n = 10) Note: One-way ANOVA was used to analyze the experimental data. Compared with the HAL group before HAL administration, *** p<0.001; compared with the HAL group after HAL administration, # p<0.05, ### p<0.001.

[0341] Example 8-4 illustrates that both Rc and Rb3 are effective components of the functional unit (Rc+Rb3).

[0342] Based on the above experimental results, an experiment was designed to further understand the relative contributions of individual Rc and Rb3 to the functional unit (Rc + Rb3). To this end, the authors compared (Rc + Rb3) and (Rb2 + Rb3) to see whether they could reverse the stiffness-increasing effect of a 36 mg / kg dose of (Rb1 + Rd) and the intensity of the effect. Based on the ratio of the individual ginsenosides in PDSC1, when the PDSC1 dose was 60 mg / kg, the dose of (Rb1 + Rd) was 36 mg / kg, the dose of (Rc + Rb3) was 16.3 mg / kg, and the dose of (Rb2 + Rb3) was 12.4 mg / kg. Accordingly, the experimental grouping and dosage design are shown in Table 29. To eliminate the influence of non-investigated factors on the experimental results, a PDSC1 control group with the corresponding dose was also established.

[0343] The experimental results are shown in Table 29. Compared with the HAL model, a 60 mg / kg dose of PDSC1 significantly shortened the two parameters reflecting stiffness, while a 36 mg / kg dose of (Rb1+Rd) significantly prolonged the head turning time and pole climbing time. This again shows that when (Rb1+Rd) in the effective dose of PDSC1 is used independently without (Rc+Rb3), it will significantly aggravate the symptoms of HAL-induced stiffness. However, based on the proportion of each individual ginsenoside in the whole composition, the pharmacodynamic strength of PDSC1 () lacking only Rb2, composed of (Rc+Rb3) added to the 36 mg / kg dose of (Rb1+Rd), is close to that of PDSC1, again indicating that Rb2 does not contribute much to the pharmacodynamics of the composition (Example 5-1). While the pharmacodynamic strength of PDSC1 () lacking only Rc, composed of (Rb2+Rb3), significantly shortened the pole climbing time, its mathematical mean was greater than that of the composition containing Rc, and it failed to significantly shorten the head turning time. These research results once again prove that the functional unit (Rc+Rb3) can transform the efficacy of the functional unit (Rb1+Rd) from aggravating stiffness to a protective efficacy of relieving stiffness, and further indicate that both Rc and Rb3 are effective components of the functional unit.

[0344] In summary, the above research results show that when used independently, the two functional units (Rb1+Rd) and (Rc+Rb3) are minimally effective or ineffective, or even exacerbate symptoms. However, when used together, their efficacy is significant, stable, and reliable. This indicates that the combined efficacy of these two functional units is not only quantitatively altered, but also qualitatively altered, and both are essential for effectively combating PD motor symptoms in PDSC1. Furthermore, this qualitative shift in efficacy further demonstrates the unique and appropriate division of labor and cooperation between the two functional units in this potent combination.

[0345] Table 29 Contribution of Rc and Rb3 to the efficacy of the functional unit (Rc+Rb3) in alleviating HAL-induced stiffness (mean ± SEM, n = 10) Note: One-way ANOVA was used to analyze the experimental data. Compared with the HAL group before HAL administration, *** p<0.001; compared with the HAL group after HAL administration, # p<0.05, ## p<0.01; compared with PDSC1, +++ p<0.001.

[0346] Summary and discussion of the research results of Examples 8-1 to 8-4:

[0347] Panaxadiol saponins Rb1, Rc, Rb3 and Rd are all effective ingredients in the panaxadiol saponin composition PDSC1 for relieving the stiffness symptoms of PD, but none of the two functional units (Rb1+Rd) and (Rc+Rb3) composed of them can represent the entire composition to relieve the stiffness symptoms of PD. The subtle division of labor and cooperation between the two (also referred to as the appropriate division of labor and cooperation) makes the full formula PDSC1 have the unique advantages of strong efficacy, stability and reliability, high safety, and a wide effective dosage range. This subtle division of labor and cooperation is reflected in the fact that (Rb1+Rd) appears to be the direct implementer of relieving stiffness, but its effective dosage range is narrow, and its dose-effect relationship (high dose is effective, medium dose exacerbates stiffness, and low dose is effective again) presents an unconventional, jumping, bidirectional change, so it cannot be developed as a drug alone; while (Rc+Rb3) seems to be a coordinator, which not only can cooperate with (Rb1+Rd) to produce a strong stiffness-relieving effect, but also can restrain its stiffness-exacerbating effect, transforming its jumping bidirectional dose-effect relationship into a stable, positive dose-effect relationship, thereby greatly expanding the effective dosage range of PDSC1 (60 mg / kg to 80 mg / kg).

[0348] In addition, the subtle division of labor and cooperation between these two functional units also fully explains that although the contents of Rb1, Rc, Rb3 and Rd in the holographic ginsenoside composition (HGC1~HGC10) and the corresponding ginsenoside composition (PDSC1~PDSC10) are quite different, they can both significantly counteract the HAL-induced stiffness symptoms in mice (Table 13 and Table 16).

[0349] Example 8-5. Exploring the contribution of the functional units (Rb1+Rd) and (Rc+Rb3) to the prevention and treatment of PD formation by PDSC1.

[0350] Based on the clarification of the importance of the combination of the two functional units (Rb1+Rd) and (Rc+Rb3) in alleviating the motor symptoms of PD in the effective composition, we used the ROT-induced rat PD model, which can reflect the root cause treatment effect, to study the significance of the combination of these two functional units in PDSC1 in preventing and treating PD formation (root cause treatment).

[0351] The experimental groups and dosage design are shown in Table 30. Based on the optimal PDSC1 dose of 40 mg / kg for this model, two dose groups were designed for the functional units (Rb1+Rd) and (Rc+Rb3): ① 40 mg / kg for each, to clarify whether any of the functional units exhibited similar effects as the full combination; and ② absolute doses of each in 40 mg / kg PDSC1, namely 24 mg / kg for (Rb1+Rd) and 16 mg / kg for (Rc+Rb3). These doses clarified the relative contribution of each functional unit in preventing and treating PD (e.g., curing the underlying cause). A PDSC1 control group was also established. The ROT-induced PD rat model, drug administration, PD clinical symptom scoring, and assessment of limb movement (forelimb stepping test and forelimb lifting test) and coordination and balance (rotarod test) were performed as previously described.

[0352] The experimental results (Table 30) showed that PDSC1 at a dose of 40 mg / kg significantly antagonized the pathological changes in various observed indicators induced by ROT, with some parameters approaching normal levels. The functional unit (Rb1+Rd) showed no protective effect at a dose of 40 mg / kg, with some indicators even numerically inferior to those in the model group. However, at a low dose of 24 mg / kg, some indicators were superior to those in the model, with the residence time on the rotarod being significantly longer than that in the high-dose group and the model group. Therefore, it can be concluded that the actual dose of (Rb1+Rd) in the full composition can partially antagonize ROT-induced PD formation. Notably, the pharmacodynamic behavior of the functional unit (Rc+Rb2+Rb3) differed significantly from that of the functional unit (Rb1+Rd). At 40 mg / kg, (Rc+Rb2+Rb3) showed superiority over the model group in all indicators only in terms of mathematical values; at 16 mg / kg, it could significantly antagonize the formation of PD in rats induced by ROT, but the mathematical values ​​of the four investigated indicators were all lower than those of the PDSC1 group, and the residence time on the rotarod was significantly shorter than that of the PDSC1 group. The above research results show that: (1) any functional unit is far from representing the whole composition to antagonize the formation and development of PD induced by ROT; (2) (Rc+Rb3) has stronger activity against the formation and development of PD induced by ROT than (Rb1+Rd), but the effective dose range is narrow, even showing a dotted distribution, which is essentially different from the effective dose range of the whole composition of 30-60 mg / kg (Example 3); (3) (Rb1+Rd) when present independently may aggravate the occurrence and development of PD or show weak protective efficacy depending on its dose, but when combined with (Rc+Rb3) to form PDSC1, it can not only synergistically produce stronger efficacy, but also greatly expand the effective dose range.

[0353] Table 30 Effects of functional units (Rb1+Rd) and (Rc+Rb3) on the prevention and treatment of PDSC1 (mean±SEM) Note: One-way ANOVA was used to analyze the experimental data. *** p<0.001; compared with ROT group, # p<0.05, ## p<0.01, ### p<0.001; compared with PDSC1 group, & p<0.05.

[0354] It can be seen that in terms of PDSC1 preventing and treating PD disease formation and progression, there is also a subtle or just right division of labor and cooperation between the two functional units (Rb1+Rd) and (Rc+Rb3). However, contrary to the relief of stiffness symptoms, it seems that (Rc+Rb3) is the direct implementer of the drug effect, while (Rb1+Rd) is the coordinator. However, there is no doubt that both are indispensable. In particular, the mutual cooperation between the two not only eliminates the drug effect defects of each other but also produces a new drug effect behavior, making the whole formula (PDSC1) powerful, stable and reliable, highly safe, and with a wide effective dosage range.

[0355] Summary and discussion of the research results of Examples 8-1 to 8-5:

[0356] Based on the research results of Example 8 above, it is further verified that Rb1, Rc, Rb3 and Rd previously discovered by the applicant are the main active ingredients of holographic ginsenosides (HGC) and the active ingredients of ginsenoside composition (PDSC), respectively. It also verifies the scientificity of dividing these four individual ginsenoside components into two functional units from the perspective of pharmacological efficacy. In particular, it reveals the subtle division of labor and cooperation between these two functional units in the process of treating PD in HGC and PDSC. For treating the symptoms, it seems that (Rb1+Rd) is the direct implementer of the pharmacological effect, while (Rc+Rb3) is the coordinator; for treating the root cause, their roles are reversed. There is no doubt that there is a division of labor and cooperation between the two. Whether it is treating the symptoms or the root cause, the two are indispensable. The cooperation between the two not only eliminates the pharmacological defects of each other but also produces a new pharmacological behavior, making the HGC or PDSC full composition powerful, stable, reliable, highly safe, and with a wide effective dosage range. This, in turn, reasonably explains that the five ratios (Rb1 / Rd, Rb1 / Rc, Rb1 / Rb3, Rc / Rb3, and (Rb1+Rd) / (Rc+Rb3) discovered by the applicant earlier jointly determine the effectiveness or ineffectiveness of HGC and PDSC and their efficacy, and that each HGC and corresponding PDSC has its own independent five ratios, or in other words, they are all independent organisms composed of (Rb1+Rd) and (Rc+Rb3) under specific content configuration conditions that can treat both the symptoms and the root cause of PD. This discovery explores the significant medicinal value of the Panax genus medicinal materials in preventing and treating PD.

[0357] Here, it should be pointed out in particular that, from the perspective of the physiology and pathology of the disease, the subtle division of labor and cooperation between the functional units (Rb1+Rd) and (Rc+Rb3) reflects their systemic treatment of the disease network, thereby producing a leap in the quantitative and qualitative changes in the efficacy of a single component and functional unit. The rigidity induced by haloperidol (HAL) is closely related to the inhibition of dopamine type 2 receptors, which leads to excessive release of acetylcholine in the striatum, especially. The mitochondrial complex enzyme I inhibitor ROT can simulate almost all the pathological mechanisms of the occurrence and development of human PD when inducing a rodent PD model, including: mitochondrial dysfunction and its malignant biochemical and cellular events such as ATP deficiency, oxidative stress damage, neuroinflammation, glial cell dysfunction, abnormal deposition of γ-synuclein and neurodegeneration. Accordingly, the applicant will continue to use PDSC1 as an example in the following examples to verify the systemic therapeutic effect of the superior composition on the disease network.

[0358] Example 9. Study on the efficacy of the superior composition in preventing and treating PD and other neurodegenerative diseases.

[0359] Brain function and health depend on the structural and functional integrity of the neurovascular unit (NVU). Furthermore, direct or indirect functional and somatic connections and interactions exist between the member cell types of the unit (including vascular endothelial cells, astrocytes, and neurons). Therefore, functional or structural impairment of any member can lead to unit pathology and related diseases. Indeed, functional and structural damage to the NVU, including cerebral microvascular damage, blood-brain barrier disruption, astrocyte dysfunction, and neurodegeneration, are common pathological features of neurodegenerative diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and are closely associated with the onset and progression of these diseases. NVU dysfunction is also closely associated with the occurrence and adverse prognosis of ischemic stroke. Mitochondrial dysfunction is considered a common pathological event in neurodegenerative diseases, which can induce and exacerbate the onset and progression of the disease. Therefore, the efficacy of the test drug in protecting the member cells of the neurovascular unit against mitochondrial dysfunction can reflect the drug's therapeutic efficacy against PD and other neurodegenerative diseases from the common mechanism and neurovascular unit level.

[0360] Therefore, studying the role of the superior ginsenoside composition and its functional units in protecting the brain cells of the various members of the neurovascular unit against ROT-induced mitochondrial dysfunction can reveal the cellular essence of the superior composition in preventing and treating PD (curing the root cause of PD) and the potential for preventing and treating other neurodegenerative diseases, as well as the appropriate division of labor and cooperation between the two main functional units in the ginsenoside composition at the cellular level, thereby enriching the scientific connotation of the superior composition in preventing and treating the occurrence and development of PD and expanding its range of symptoms for preventing and treating neurodegenerative diseases.

[0361] Based on the pharmacodynamic characteristics of the ginsenoside composition PDSC1 in preventing and treating the ROT-induced PD rat model and the subtle / appropriate division of labor and cooperation between its two functional units, the applicant believes that PDSC1 can protect the member cells of the NVU, and the cell types that its two functional units prioritize protecting may be different. However, it is currently unknown how the different member cells in the NVU interact with each other during the occurrence and development of PD and other neurodegenerative diseases, such as which one becomes ill first and how the lesions affect other member cells. Therefore, it is impossible to curb the disease in the early stages or embryonic stage by precisely targeting upstream pathological events or the most vulnerable member cells, nor is it possible to accurately understand the mechanism of action of the superior composition, especially the appropriate division of labor and cooperation of its functional units at the neurovascular unit level.

[0362] Therefore, the applicant will first compare the vulnerability of the three main member cell types of the NVU to ROT inhibition of mitochondrial complex I to reveal the most vulnerable member cells that may exist in the unit; then, explore whether the most vulnerable cell type releases inflammatory factors or toxic substances after being damaged or diseased, thereby reducing the toxicity of surrounding cells to the loss of complex I function; finally, study the protective effect of PDSC1 and its functional units on the neurovascular unit and its mechanism of action.

[0363] Example 9-1. Comparative study of the vulnerability of three member cells of NVU to ROT inhibition of mitochondrial complex I and the protective effect of PDSC1.

[0364] The vulnerability of three NVU cell members to ROT inhibition of mitochondrial complex I was compared to reveal the most vulnerable cell member of the unit. Human brain microvascular endothelial cells (HBMECs), primary rat astrocytes (ASCs), and highly differentiated PC12 cells, a dopamine neuron model, were cultured using conventional methods. PC12 cells were induced to differentiate into dopamine neurons (or simply neurons) using neurotrophic factor (NGF) using conventional methods. Twenty-four hours after seeding, ROT, an inhibitor of mitochondrial complex I, was added to the culture medium at varying concentrations, with 5 wells (n=5) per concentration. Cultures were then continued for 72 hours. Cell viability was measured using the sulforhodamine B (SRB) method, and the inhibition rate (%) of ROT on cell viability was calculated. As shown in Table 31, ROT reduced the viability of endothelial cells, astrocytes, and dopamine neurons in a concentration-dependent manner.

[0365] Table 31 Inhibition rate (%) of rotenone (ROT) on the viability of three member cells of the neurovascular unit (NVU) Compared with normal control: *p<0.05, **p<0.01, ***p<0.001; n=5.

[0366] Based on the dose-effect relationship data of each cell, the IC of ROT for each different cell was calculated using SPSS.20 software. 50 The (half-maximal inhibitory concentration) values ​​were: 230.56 nM for human brain microvascular endothelial cells (HBMEC), 1980 nM for astrocytes (ASC), and 549.33 for dopamine neurons (PC12) (Table 32).

[0367] The results of the study indicate that, in the neurovascular unit, brain microvascular endothelial cells are the most sensitive / vulnerable to functional loss of mitochondrial complex enzyme I, followed by neurons, while astrocytes have a strong ability to cope with functional loss of mitochondrial complex enzyme I. The results of the study are consistent with the common presence of brain microvascular damage in PD patients and the fact that a type of PD patient clinically has vascular damage as the main cause (called vascular PD), indicating that protecting brain vascular endothelial cells has important therapeutic value in preventing and treating PD. In particular, the results of the study provide new clues for the subsequent revelation of the role of the interaction between the member cells in the neurovascular unit in the occurrence and development of PD, and provide clues for the subsequent in-depth revelation of the mechanism of action of the ginsenoside superior composition in treating both the root cause and the symptoms of PD, as well as the scientific nature of the perfect interaction between its two functional units and the configuration of the effective ingredient content.

[0368] Table 32 The half-maximal inhibitory concentration (IC) of rotenone on the three member cells of the neurovascular unit (NVU) 50 )(n=5)

[0369] Next, we observed the protective effect of the ginsenosides composition PDSC1 on the member cells of the neurovascular unit against the mitochondrial complex enzyme I inhibitor ROT, in order to clarify whether the protective effect of the composition on the member cells was consistent or different. The test cells were cultured using conventional methods, and the IC values ​​of ROT of each member cell were used. 50 The cells were treated with the concentration of the maximum value for 48 hours to induce cell damage. Different concentrations of PDSC1 were applied before ROT. A normal control group and a ROT control group were set up at the same time, and the cell viability was determined by SRB.

[0370] Table 33 The effective composition PDSC1 protects neurovascular unit member cells against rotenone toxicity Compared with ROT control: *p<0.05, **p<0.01, ***p<0.001, n=5.

[0371] As shown in Table 33, within the concentration range of 1.25 to 55.0 μM, PDSC1 significantly protected human brain microvascular endothelial cells (HBMECs), astrocytes (ASCs), and dopamine neuron cell model PC12 cells against ROT-induced cell damage. The optimal concentration was between 1.25 and 25 μM, and no significant differences were observed between the member cells. This indicates that the superior composition can protect all member cells of the neurovascular unit, including the most vulnerable brain microvascular endothelial cells, against cytotoxicity induced by mitochondrial complex enzyme I dysfunction or deficiency, and has a wide effective concentration range. Mitochondrial complex enzyme I dysfunction or deficiency is an important environmental and intrinsic risk factor for PD, and mitochondrial dysfunction is a major cause of neurodegeneration. It should also be noted that mitochondrial complex enzyme I dysfunction or deficiency is also common in the brains of patients with Alzheimer's disease and is involved in the progression of the disease. Therefore, the research results strongly support the superior composition's role in curing the root cause of PD disease by combating environmental and intrinsic risk factors, and also support its medical use in the treatment of Alzheimer's disease.

[0372] Next, the effect of PDSC1 at a concentration of 25 μM against ROT-induced HBMEC apoptosis was further observed. The cell apoptosis rate was determined using a conventional commercial kit. As shown in Table 34, ROT (100 nM) treatment for 48 hours induced apoptosis in nearly 30% of cells; PDSC1 not only reduced the apoptosis rate of cells in the basal state (compared with the normal control group), but also significantly antagonized ROT-induced endothelial cell apoptosis. The results of the study demonstrate the safety and effectiveness of PDSC1 in protecting vascular endothelial cells against PD risk factors (mitochondrial complex enzyme I deficiency).

[0373] Table 34 Effect of Panaxadiol Saponin Superior Composition PDSC1 on ROT-induced apoptosis of human cerebral vascular endothelial cells PDSC1: Panaxadiol saponin composition 1; ROT: Rotenone; *** p<0.001 (vs. normal control group); ### p<0.001 (vs. ROT group); n=5.

[0374] Example 9-2. The relationship between the pharmacological effect of the ginsenoside composition in protecting the neurovascular unit and its efficacy in preventing and treating the occurrence and development of PD.

[0375] To further elucidate the relationship between the pharmacological effects of the superior ginsenoside composition in protecting the neurovascular unit and its efficacy in preventing and treating the occurrence and development of PD, a comparative study was conducted on the effects of the superior and ineffective compositions in protecting the neurovascular unit against ROT cytotoxicity in a rat model of PD induced by ROT. The experimental data (Table 35) showed that there was no significant difference in the protective effects of the superior, effective, and ineffective compositions on human brain microvascular endothelial cells (HBMECs), astrocytes (ASCs), and dopamine-producing PC12 cells, and no significant difference was observed in the overall protection rates of various cell types.

[0376] Table 35 Holographic ginsenosides protect neurovascular unit member cells against ROT toxicity Compared with the normal control group: ***p<0.001; compared with the ROT group: ### p<0.001; n=5.

[0377] Since the vicious cycle formed by the interaction between the member cells of the neurovascular unit leads to the development of PD induced by insufficient function of mitochondrial complex enzyme I, the uniform protection of each member cell may be the key to determining whether the holographic ginsenoside composition (HGC) and the corresponding ginsenoside composition (PDSC) are effective. Based on this, the relationship between the total protection rate (%) of each ginsenoside composition for the three member cells, the difference between the protection rates of the three cells, and the sum of the differences (referred to as protection discreteness) and the overall efficacy was further analyzed. As shown in Table 36, the protective effect of the superior composition on the three member cells is the most uniform, which is manifested in the smallest difference between the maximum protection rate and the minimum protection rate, the small difference between the intermediate value and the two end values, and the smallest protection discreteness; the ineffective composition has the largest discreteness of the protection rate of the three member cells, while the effective composition has a discreteness of the protection rate of the three member cells between the two. In particular, the ineffective composition PDSC1-1 has the strongest protective effect on vascular endothelial cells (HBMEC), while the effective composition PDSC1-2 has stronger protective effects on vascular endothelial cells (HBMEC) and astrocytes (ASC) than the superior composition PDSC1, but its effect on the neural cell model PC12 cells is weaker than the superior composition. However, the two effective compositions PDSC1-2 and PDSC1-4 can evenly protect vascular endothelial cells (HBMEC) and astrocytes (ASC). Since astrocytes have the function of protecting nerves, protecting these two cell types at the same time can be converted into a neuroprotective effect under overall conditions.

[0378] Table 36 Relationship between overall efficacy and protective effect on neurovascular unit member cells

[0379] The above research results show that uniform protection of each member cell type in the neurovascular unit is crucial for preventing and treating the occurrence and development of PD induced by mitochondrial complex enzyme I functional deficiency, and the superior composition can uniformly protect each member cell. On the other hand, looking at the five ratios of these superior compositions (PDSC1) and their PDSC1-derived compositions (PDSC1-1 to PDSC1-6) and their efficacy against ROT-induced PD in rats, it can be seen that slight changes in the five ratios will lead to a shift in the protection of the member cell types of the neurovascular unit, thereby affecting the overall strength or absence of efficacy. This further reveals the mystery of how the five ratios of the superior composition are converted into efficacy for preventing and treating the occurrence and development of the ROT-induced PD model in rats.

[0380] Example 9-3. Protective effects of the functional units (Rb1+Rd) and (Rc+Rb3) on neurovascular unit member cells.

[0381] Targeting PDSC1, a single component combination was used to reconstitute PDSC1 and its two functional units (Rb1+Rd) and (Rc+Rb3). Using ROT-induced PD cell models of human brain microvascular endothelial cells (HBMEC), rat primary astrocytes (ASC), and dopamine neuronal cell model P12 cells, the pharmacodynamics of PDSC1, reconstituted PDSC1, the two functional units (at the same dose as the full composition and the actual dose in the composition), and the combined efficacy of the two functional units at the actual dose were compared. The results revealed the similarities and differences between the full composition and the functional units, as well as the similarities and differences between the functional units. The experimental dose of PDSC1 was set at 25 μM; based on the proportions of the five components in PDSC1 in the total ginsenosides of 28.14% Rb1, 12.95% Rc, 8.02% Rb2, 16.48% Rb3, and 27.44% Rd, PDSC1 and the functional units were constructed using single components (Table 37). Cell culture, drug treatment, and cell viability assays were the same as before.

[0382] As shown in Table 37, PDSC1 recombined with four single ginsenosides Rb1, Rc, Rb3 and Rd and the original PDSC1 can significantly antagonize the decreased viability of human brain microvascular endothelial cells (HBMEC), rat primary astrocytes (ASC) and dopamine neuron P12 cells induced by rotenone (ROT), and the two have the same efficacy, indicating that these four ginsenosides can reconstruct the full activity of PDSC1.

[0383] Table 37 Effects of PDSC1 and its functional units against rotenone-induced decrease in cell viability Compared with the normal control group: ***p<0.001; compared with the ROT model group: # p<0.05, ## p<0.01,### p<0.001; compared with PDSC1 group: & p<0.05; n=5.

[0384] In particular, the study found that at both the dose equivalent to the full composition (25 μM) and the actual dose in the composition (13.9 μM), the functional unit (Rb1+Rd) significantly protected HBMEC, ASC, and dopamine neuronal P12 cells, but the potency of their effects was significantly lower than that of the full composition PDSC1 and recombinant PDSC1. Under corresponding conditions, (Rc+Rb3) also significantly protected these three cell types, but its potency was also significantly lower than that of the full composition PDSC1 and recombinant PDSC1. However, the combined protective effect of these two functional units on the three member cells was the same as that of PDSC1. These data indicate that both (Rb1+Rd) and (Rc+Rb3) are functional units of PDSC1 that protect member cells of the neurovascular unit and that neither can replace the full composition.

[0385] It is also important to note that the research data further indicate that: under both dosage conditions, the protective intensity of (Rb1+Rd) on astrocytes (ASC) is better than that of (Rc+Rb3), and at the actual dose in the full composition (13.9μM), its efficacy is close to that of the full composition; while the effect on protecting vascular endothelial cells (HBMEC) is just the opposite, that is, the efficacy of (Rc+Rb3) is better than that of (Rb1+Rd), and at the actual dose in the full composition (7.36μM), its efficacy is close to that of the full composition; however, at both concentrations, the protective effect of (Rc+Rb3) on dopamine neuronal PC12 cells is better than that of (Rb1+Rd), and the combination of these two functional units at the actual concentration in the full composition fully reproduces the efficacy of the full composition. These findings suggest that (Rb1+Rd) and (Rc+Rb3) are the primary active components of PDSC1 that protect PD astrocytes and vascular endothelial cells, respectively, with the latter being more protective of dopamine neurons. In particular, the two can synergistically protect the various cell types within the neurovascular unit. Therefore, when combined in an appropriate ratio, they can maximize protection for the various cell types within the neurovascular unit.

[0386] The above research results show that there are two different functional units in the ginsenoside composition PDSC1 that protect the neurovascular unit, and they have both common functions and their own division of labor. Their commonality is that they have a protective effect on the three member cells of the neurovascular unit, but the functional unit (Rb1+Rd) has a prominent role in protecting astrocytes (ASC), while the functional unit (Rc+Rb3) has a stronger protective effect on brain vascular endothelial cells (HBMEC) and dopamine neurons. It can be seen that the effective composition ensures that it can protect each member cell of the neurovascular unit to the greatest extent from the configuration of active ingredients and content.

[0387] Combined with the results from the PD animal model, (Rb1+Rd) is the main active component against motor symptoms caused by dopamine signaling deficiency, while (Rc+Rb3) is the main active component against the formation and progression of PD induced by ROT. These findings suggest that ASC dysfunction is associated with PD motor symptoms, and that dysfunction or degeneration of brain microvascular endothelial cells is closely related to the formation and progression of PD. Indeed, ASC is crucial for maintaining the homeostasis of the extracellular excitatory neurotransmitter glutamate in the striatum and other brain regions. Elevated extracellular glutamate levels and its excitotoxicity caused by ASC dysfunction or excessive release from nerve endings are associated with neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and epilepsy. Furthermore, striatal glutamate hyperexcitability is closely associated with the progression of PD, its motor symptoms, and dyskinesias induced by levodopa treatment. Neurological functional and structural degeneration and cerebral microvascular damage (including endothelial cell damage and blood-brain barrier impairment) are common pathological mechanisms underlying the development and adverse outcomes of PD, AD, cerebral amyloid angiopathy, vascular dementia, and other neurodegenerative diseases, as well as stroke. Therefore, our findings support the medical use of the panaxadiol saponin combination for the prevention and treatment of neurological disorders, neurodegenerative diseases, and the development and adverse outcomes of stroke, from the perspective of protecting the neurovascular unit.

[0388] Example 10. In an environment where mitochondrial complex enzyme I is dysfunctional or absent, diseased vascular endothelial cells release inflammatory factors and drive astrocytes to transform into A1 toxic cell types, thereby leading to the expansion and depth of the disease network. The effective composition starts by protecting endothelial cells to counteract the formation and development of the PD disease network involving endothelial cells, astrocytes and neurons induced by the dysfunction or absence of complex enzyme I.

[0389] As mentioned above, although it is known that the functional and structural degeneration or damage of the neurovascular unit (NVU) is closely related to neurodegenerative diseases, stroke and its sequelae, it is still unknown how the different member cells in the NVU interact with each other during the occurrence and development of related diseases, such as which member cells become ill first and how the lesions affect other member cells. Therefore, it is impossible to curb the disease in the early stages or budding state by precisely targeting upstream pathological events or the most vulnerable member cells, and to understand the relevant action mechanisms of effective compositions.

[0390] The results of Example 9 clearly show that brain microvascular endothelial cells are the most sensitive or vulnerable cells in the NVU to the loss of complex enzyme I function caused by ROT, and PDSC1 can protect the core member cells of the NVU. On this basis, we further explore whether the diseased endothelial cells release pathological products such as inflammatory factors, thereby making the surrounding astrocytes and neurons vulnerable to the existing low or missing function of complex enzyme I? And damaged astrocytes can further aggravate neural damage? Accordingly, PDSC1 protects the NVU member cells against ROT toxicity, and thus can prevent and control the formation and deep progression of ROT-induced PD disease network? To this end, the following studies were carried out in sequence to verify these assumptions.

[0391] Example 10-1. Does culture medium containing ROT-induced pathological endothelial cells render astrocytes and neurons vulnerable to ROT?

[0392] The apoptotic effects of conditioned medium from endothelial cells cultured for 48 hours with a low concentration of ROT (100 nM is toxic only to endothelial cells) (ECM-ROT) and conditioned medium supplemented with 100 nM ROT (ECM-ROT+ROT) on astrocytes (ASCs) and dopamine neurons (PC12 cells) were compared. Simultaneously, conditioned medium from endothelial cells protected by PDSC1 was studied in parallel, with the corresponding groups including PDSC1+ROT-ECM and PDSC1+ROT-ECM+ROT. Corresponding control groups included a normal control, ROT, normal endothelial cell-conditioned medium (ECM), and ECM-ROT. Conditioned medium was prepared using conventional methods: The culture medium from HBMECs treated with ROT for 48 hours was filtered through a 3 kDA ultrafiltration tube to remove residual ROT. Proteins enriched on the membrane, including inflammatory factors, were eluted and concentrated by conventional methods, and then diluted to obtain the specific conditioned medium (ECM-ROT) used to culture astrocytes and neurons for 48 hours. Annexin V fluorescence double staining apoptosis kit was used to determine the apoptosis rate of cells in each group.

[0393] The experimental results are shown in Table 38: Low-dose rotenone (100 nM) only caused 14.00% astrocyte apoptosis, but ROT (100 nM)-conditioned medium from HBMECs induced 27.00% astrocyte apoptosis. Consistently, the above two conditions resulted in 19.00% and 38.00% apoptosis in PC12 cells, respectively. Thus, the toxicity of medium from HBMECs conditioned medium to astrocytes and PC2 cells was greater than that of 100 nM rotenone. In particular, when 100 nM ROT was added to HBMEC-conditioned medium, the astrocyte apoptosis rate reached 56.00%, significantly higher than that in the control group given only 100 nM Rot (p < 0.001) and the HBMEC-conditioned medium group (ROT-ECM). Similar results were observed in PC12 cells, with the apoptosis rate in the ROT-ECM+ROT group reaching 71.87%, significantly higher than that in the ROT and ROT-ECM groups (p<0.001). The apoptosis rates of astrocytes and neurons in PDSC1-protected endothelial cell-conditioned medium (PDSC1+ROT-ECM) and in PDSC1+ROT-ECM+ROT plus 100nM ROT (PDSC1+ROT-ECM+ROT) were significantly lower than those in the ECM-ROT and ECM-ROT+ROT groups.

[0394] Table 38 Cytotoxicity of ROT-injured vascular endothelial cell conditioned medium on astrocytes and neurons and the protective effect of PDSC1 ROT-ECM: conditioned medium of rotenone-injured brain microvascular endothelial cells; *** p<0.001 (vs. normal control group); ### p< 0.001 (vs. ROT group); ++p<0.01 (vs. ROT group); && p<0.01 (vs. ROT-ECM group); @@@ p<0.001 (vs. ROT+ROT-ECM group); n=5.

[0395] The above results prove that ROT-injured HBMECs release toxic substances (or inflammatory factors) that can significantly damage surrounding astrocytes and neurons and greatly increase the sensitivity of astrocytes and neurons to ROT toxicity; PDSC1 protects endothelial cells against ROT toxicity and inhibits their release of toxic substances, thereby avoiding direct damage to astrocytes and neurons by diseased endothelial cells and significantly increasing the toxicity of rotenone to these two types of cells.

[0396] Example 10-2. Vascular endothelial cells with insufficient or absent mitochondrial mitochondrial coenzyme I function increase the vulnerability of astrocytes and neurons to coenzyme I deficiency by activating NF-kBp65 and releasing inflammatory factors; PDSC1 can inhibit the activation of p65 and the release of inflammatory factors caused by insufficient or absent coenzyme I function, thereby maintaining the neurovascular unit exposed to PD risk factors from developing the disease.

[0397] It is known that activation of inflammatory pathways usually occurs in diseased vascular endothelial cells. Therefore, the applicant believes that ROT-induced diseased vascular endothelial cells can release inflammatory factors to make surrounding cells and neurons vulnerable to insufficient or missing mitochondrial complex I function. To verify this hypothesis, a comparative study was first conducted to study whether 100nM ROT selectively activates the NF-κB inflammatory signaling pathway in endothelial cells of the neurovascular unit (NVU) and releases a large number of pro-inflammatory factors into the culture medium. At the same time, the possible anti-ROT-induced inflammatory response of 25μM PDSC1 was observed.

[0398] NVU member cells, including mouse microvascular endothelial cells (bEnd.3), primary mouse astrocytes (ASCs) and microglia (MGAs), and dopamine neuron PC12 cells, were cultured using conventional methods. When cell abundance reached 70-80%, they were exposed to 100 nM ROT for 48 hours. Cells were harvested and the mRNA levels of phosphorylated p65 (p-NF-κB p65), an indicator of NF-κB inflammatory signaling pathway activation, and downstream inflammatory factors, including TNF-α, IL-1β, IL-6, iNOS, ICAM, and VCAM, were measured. Protein levels of these inflammatory factors were also measured in the culture medium of the activated member cells. p-p65 levels were analyzed by Western blotting, and mRNA and protein levels of these inflammatory factors were analyzed by qPCR and ELISA kits, respectively. NO levels were analyzed using kit-based methods.

[0399] The results showed that 100 nM ROT selectively increased p-NF-κB p65 levels in each member cell type (Figure 1), accompanied by significant increases in intracellular TNF-α, IL-1β, IL-6, iNOS, ICAM, and VCAM mRNA levels (Table 39) and in the culture medium (Table 40). PDSC1 almost completely antagonized ROT's upregulation of inflammatory cytokine and adhesion molecule mRNA levels in endothelial cells and their release of inflammatory factors into the culture medium. However, PDSC1 also slightly increased iNOS and its product, NO, in normal endothelial cells, triggering a cellular inflammatory response, thus helping to alleviate vascular tension.

[0400] Table 39 PDSC1 inhibits rotenone (ROT)-upregulated mRNA levels of proinflammatory cytokines and adhesion molecules in endothelial cells CON: normal control group; PDSC1: ginsenoside composition 1; *** p<0.001(vs.CON); ### p<0.001 (vs. ROT); n=5.

[0401] These findings suggest that low-concentration rotenone (ROT, 100 nM, which inhibits mitochondrial mitochondrial enzyme I, leading to its deficiency or even absence) selectively activates p65 in endothelial cells of the neurovascular unit (NVU), leading to the release of adhesion molecules and pro-inflammatory cytokines. PDSC1 almost completely maintains the homeostasis of p65 activity in endothelial cells with mitochondrial ...

[0402] Table 40 PDSC1 inhibits rotenone (ROT)-induced pro-inflammatory cytokines released by endothelial cells CON: normal control group; PDSC1: ginsenoside composition 1; *** p<0.001(vs.CON); ### p<0.001 (vs. ROT); n=5.

[0403] On this basis, we further investigated whether the inflammatory factors released by these endothelial cells were a key factor in the vulnerability of other NVU member cells to the previously innocuous mitochondrial complex I deficiency caused by the conditioned medium from diseased endothelial cells. To this end, we used commercially available inflammatory factors to reconstitute the inflammatory environment of the conditioned medium from diseased endothelial cells and observed whether they could reproduce the pathological effects of the toxic conditioned medium from Example 10-1 on astrocytes and neurons. We then used small interfering RNA (siRNA) to selectively inhibit p-65-mediated inflammatory activation in endothelial cells to counteract our findings.

[0404] According to the levels of pro-inflammatory factors in the culture medium of ROT-treated endothelial cells shown in Table 41, the conditioned medium of vascular endothelial cells treated with 100nM ROT for 48 hours containing 5μg / ml TNF-α, 15μg / ml IL-1β and 10μg / ml IL-6 was reconstituted with commercial inflammatory factors, and the effects of inducing apoptosis of astrocytes and dopamine neurons PC12 cells alone or in combination with 100nM ROT were observed.

[0405] As shown in Table 41, the conditioned medium reconstituted with pro-inflammatory factors completely reproduced the pathological effects of the culture medium in which vascular endothelial cells were treated with 100 nM ROT for 48 hours, which was manifested in that the conditioned medium reconstituted with pathogenic inflammatory factors itself reduced the cell viability of astrocytes and PC12 cells to a certain extent, while greatly increasing the toxicity of ROT to these two cells.

[0406] Table 41 Proinflammatory factors in rotenone-damaged conditioned medium can completely simulate the toxicity of conditioned medium to astrocytes CON: normal control group; ROT: rotenone; *** p<0.001(vs.CON); ### p<0.001 (vs. ROT 100nM); n=5.

[0407] As shown in Table 42, the conditioned medium of p65-inhibited endothelial cells treated with 100 nM ROT for 48 h did not increase the apoptosis rate of astrocytes (ASC) and PC12 cells, nor did it increase the apoptosis rate of these two cells induced by low concentrations of ROT.

[0408] Conclusion and Discussion

[0409] The above research results, combined with the research results of Example 10-1, show that 100 nM ROT, which is toxic only to endothelial cells, selectively activates the pro-inflammatory NF-kB pathway of endothelial cells in the NVU and causes them to release adhesion molecules (including ICAM-1, VCAM-1) and inflammatory factors (including TNF-α, IL-1β, IL-6), among which the combined effects of TNF-α, IL-1β and IL-6 are sufficient to make astrocytes and dopamine neurons extremely vulnerable to the originally non-pathogenic mitochondrial complex enzyme I deficiency.

[0410] In addition, white blood cells in the blood interact with endothelial cells and infiltrate through the blood-brain barrier to cause inflammatory infiltration, further exacerbating the inflammatory response in the brain and various neurodegenerative pathological processes including PD and AD. This process is driven by adhesion molecules (ICAM-1, VCAM-1, etc.) on the surface of brain vascular endothelial cells. Therefore, the surface adhesion molecules upregulated by endothelial cells with insufficient mitochondrial complex enzyme I function (PD risk factor) play the role of luring wolves (white blood cells) into the room (brain), thereby further complicating the pathological mechanism of PD.

[0411] The potent panaxadiol saponin composition, PDSC1, protects vascular endothelial cells with insufficient mitochondrial complex enzyme I function, inhibits the NF-κB p65 pathway and the release of adhesion factors and inflammatory factors, thereby maintaining the functional and structural homeostasis of the neurovascular unit in cells exposed to PD risk factors. Since microRNAs (miRNAs) regulate the expression of these adhesion molecules through two different main mechanisms, namely by regulating the pro-inflammatory NF-κB pathway (controlling its transcription) and directly targeting them, the fact that PDSC1 completely inhibits the upregulation of adhesion molecules by endothelial cells with insufficient mitochondrial complex enzyme I function also indicates that PDSC1 has a role in maintaining the functional homeostasis of miRNAs. It should be pointed out here that PDSC1's role in moderately increasing the level of NO released by endothelial cells with normal and deficient complex enzyme I function has multiple biological activities and pharmacological effects, including: preventing and relieving vascular tension, thereby improving the supply of oxygen and nutrients to the central nervous system; protecting the functional integrity of the neurovascular unit, preventing the activation of microglia, stimulating glycolysis of astrocytes, and increasing mitochondrial biogenesis, preventing the accumulation of neuronal amyloid protein and the formation of neurofibrillary tangles, which are markers of Alzheimer's disease pathology (Circ J. 2016; 80(7): 1499-503; Stroke. 2023; 54(3): 686-696.). In Examples 10-3 to 10-5, we demonstrated in cell models the function of PDSC1 in protecting astrocytes and their ability to phagocytose / clear toxic proteins such as Aβ. In Example 10-6, we further demonstrated that PDSC1 protects the integrity of the neurovascular unit, prevents microglial activation, and abnormal deposition of γ-synuclein (γ-syn) in a rat PD model (astrocyte dysfunction leading to its inability to be cleared and deposited, a key pathological mechanism of PD).

[0412] Table 42 Inhibition of endothelial cell p65 by siRNA can eliminate the toxicity of ROT-treated endothelial cell conditioned medium to astrocytes and neurons CON: normal control group; ROT: rotenone; ROT-ECM: conditioned medium of brain microvascular endothelial cells treated with rotenone (ROT); ROT-sip65-ECM: conditioned medium of brain microvascular endothelial cells treated with siRNA p65 combined with rotenone (ROT); *** p < 0.001 (vs. CON); ### p<0.001 (vs. ROT 100nM); &&& p<0.001(vs.ROT-CEM+ROT); n=5.

[0413] Example 10-3. Lesioned endothelial cells release inflammatory factors that induce neurotoxic A1 astrocyte type.

[0414] Astrocytes (ASCs) in the A2 state possess neuroprotective properties, whereas ASCs in the A1 state not only lose their neuroprotective functions and maintain microenvironmental homeostasis, such as neurotransmitter homeostasis, but also release proinflammatory cytokines, leading to neuroinflammation. Increased A1 cell numbers are closely associated with Parkinson's disease and Alzheimer's disease, leading to the term "neurotoxic A1 cells." Inflammatory factors released by microglia are known to induce the conversion of A2 cells to the A1 state, leading to the hypothesis that inflammatory factors released by endothelial cells could also induce A1 formation, further deepening and widening the pathological network of Parkinson's disease. Similarly, PDSC1 protects endothelial cells with complex enzyme I deficiency, thereby preventing endothelial cell-induced A1 formation and its malignant pathological consequences. To test this hypothesis, the effect of ASCs treated with 100 nM ROT-induced lesions or PDSC1-protected endothelial cell-conditioned medium (ROT-ECM) for 48 hours on the induction of A1 cell formation was investigated. A control group (CON), a control group (ROT) treated with 100 nM ROT, and a control group (ECM) conditioned by normal endothelial cells were also established. Detection indicators include A1 cell-specific gene transcripts H2-D1 and H2-T23, A2 cell-specific products sphk1 and B3gnt5, ASC-specific protein GFAP, and A1 cell-specific protein C3d. Quantitative polymerase chain reaction (qPCR) was used to measure the transcript levels of selected genes.

[0415] The results (Table 43) showed that ROT-induced endothelial cell conditioned medium (ROT-ECM) significantly increased the mRNA levels of H2-D1 and H2-T23, characteristic of A1, and significantly decreased the mRNA level of B3gnt5, characteristic of A2. Low-concentration ROT (100 nM) only slightly increased the mRNA level of H2-D1 and significantly increased the mRNA levels of sphk1 and B3gnt5. Consistent with the protective effect of PDSC1 on endothelial cells against ROT toxicity, the conditioned medium of ROT-treated endothelial cells protected by PDSC1 (PDSC1-ROT-ECM) had the same effect as low-concentration ROT (ROT), slightly increasing the A1 phenotype while significantly increasing the A2 phenotype. The results of the study showed that the culture medium of diseased endothelial cells can convert normal astrocytes into the neurotoxic A1 state, while the low concentration of ROT without cytotoxicity promotes the transformation of normal astrocytes into the neuroprotective A2 state. PDSC1 can inhibit the release of substances that promote the formation of the A1 phenotype by endothelial cells with insufficient complex enzyme I function, while increasing their release of substances that promote the formation of the A2 phenotype.

[0416] Table 43 ROT induces the release of inflammatory factors from lesioned endothelial cells and induces the A1 phenotype of neurotoxic astrocytes CON: normal control group; ROT: rotenone; ROT-ECM: rotenone-treated brain microvascular endothelial cell-conditioned medium; * p<0.05, *** p<0.001(vs.CON); ### p<0.001 (vs.ROT-ECM); n=5.

[0417] Conclusion and Discussion:

[0418] Combined with the research results of Examples 10-1 to 10-3, the applicant found that when exposed to low concentrations of rotenone (inhibiting the function of complex enzyme I) that only damages endothelial cells, among the members of the neurovascular unit, including microglia, only the pro-inflammatory NF-κB pathway of endothelial cells is activated and secretes inflammatory factors such as IL-1β, IL-6 and TNF-α, and the combined action of these three pro-inflammatory factors is sufficient to induce the A1 phenotype and weaken the A2 phenotype; the ginsenoside effective composition PDSC1 can protect endothelial cells against the impact of insufficient complex enzyme I function, greatly slowing down the activation of the pro-inflammatory NF-κB pathway and the secretion of pro-inflammatory factors, thereby preventing the formation of A1 cells and promoting the formation of A2 cells.

[0419] It is known that proinflammatory cytokines derived from pathologically activated microglia can induce the formation of A1 cells, and A1 cell formation is considered an important pathogenic mechanism in neurodegenerative diseases, including AD and PD. The findings here indicate that diseased endothelial cells are also the source of A1 formation, and in the early stages of PD (where mitochondrial complex enzyme I deficiency is the primary cause), diseased endothelial cells may be the sole trigger of A1 cell formation, which updates our understanding of the pathogenesis and progression of PD and other neurodegenerative diseases. Furthermore, cerebral microvascular destruction is a common feature of various neurodegenerative diseases, including AD and PD. The pathological effects of cerebral microvascular destruction on neurodegenerative diseases have previously been understood primarily from the perspectives of energy, nutrient and oxygen supply, and the blood-brain barrier. Our findings further reveal the mechanism by which inflammatory endothelial cells induce and promote neurodegenerative diseases by inducing A1 cells and adhesion molecules to attract peripheral leukocytes into the brain. Therefore, our research findings indicate that protecting brain vascular endothelial cells is a promising new strategy for preventing and treating neurodegenerative diseases including AD and PD and sequelae of stroke, and PDSC1 and other effective compounds can implement this therapeutic strategy.

[0420] Example 10-4. Diseased endothelial cells poison neurons and increase the vulnerability of astrocytes to cytotoxic complex I deficiency by inducing the formation of neurotoxic A1 cells and weakening the neuroprotective A2 cells; PDSC1 protects endothelial cells to avoid A1 cell formation and enhances the neuroprotective effect of A2 cells.

[0421] Based on the results of Example 10-3, the levels of pro-inflammatory factors (including TNF-α, IL-1β and IL-6) and anti-inflammatory factors (including IL-4 and IL-10) released by A1 cells into the culture medium induced by 100 nM ROT-treated endothelial cells conditioned medium (ROT-ECM) were further determined. At the same time, corresponding control groups were set up, including normal cultured astrocytes (CON), 100 nM ROT-treated astrocytes (ROT, actually A2), and conditioned medium (ECM) of normal endothelial cells.

[0422] As shown in Table 44, the conditioned medium of ROT-treated endothelial cells (ROT-ECM) induced A1 cells to release proinflammatory factors TNF-α, IL-1β, and IL-6 into the culture medium at levels significantly higher than those of other control groups, but the levels of anti-inflammatory factors IL-4 and IL-10 were significantly lower than those of other control groups, while the ability of A2 cells to release anti-inflammatory factors showed an increasing trend. This indicates that A1 cells have lost the ability of normal astrocytes to release anti-inflammatory factors, while releasing a large amount of proinflammatory factors. Importantly, the conditioned medium of endothelial cells protected by PDSC1 (PDSC1-ROT-ECM) did not significantly increase the level of proinflammatory factors secreted by astrocytes, but instead showed a trend to increase the secretion of anti-inflammatory factors. This effect of PDSC1 is consistent with the effect of its conditioned medium (PDSC1-ROT-ECM) in inhibiting the formation of the A1 phenotype and tending to promote the formation of A2 (Table 45).

[0423] Table 44 Characteristics of inflammatory cytokines released by A2 cells induced by ROT and A1 cells induced by ROT-treated endothelial cell culture medium CON: normal control group; ROT: rotenone; ROT-ECM: conditioned medium of brain microvascular endothelial cells treated with rotenone; * p<0.05, *** p<0.001(vs.CON); ### p<0.001 (vs. ROT-ECM-induced A1); n=5.

[0424] Next, the effects of A1 cell conditioned medium (A1CM) and A2 cell conditioned medium (A2CM) on inducing apoptosis of PC12 cells by themselves, and their effects on inducing apoptosis of PC12 cells by combining with 100 nM Rot, A1CM (A1 induced by ROT-ECM in Table 44) (ROT+A1CM) and A2CM (A2 induced by ROT in Table 44) (ROT+A2CM), respectively, were determined. At the same time, corresponding control groups were set up, including normal control (CON), 100 nM ROT control (ROT), and conditioned medium of astrocytes treated with PDSC1-protected endothelial cell culture medium in Table 44, namely PDSC1-ACM and ROT+PDSC1-ACM. The results are shown in Table 45. The apoptosis rate of PC12 cells induced by A2 cell culture medium combined with ROT was significantly lower than that induced by 100 nM ROT, indicating that A2 cells can release neuroprotective substances. The apoptosis rate induced by A1 cell conditioned medium alone (44.03%) was significantly higher than that induced by 100 nM ROT (18.26%), and significantly increased the apoptosis rate of PC12 cells induced by 100 nM ROT (69.43%). This indicates that the inflammatory factors released by A1 cells are sufficient to induce apoptosis of peripheral neurons, and that neurons with insufficient complex enzyme I function are highly susceptible to A1 toxicity. The apoptosis rate of neurons induced by the conditioned medium of astrocytes treated with PDSC1-protected endothelial cell culture medium (PDSC1-ACM) was 13.96%, which was significantly lower than that induced by the A1 cell conditioned medium (A1CM). The neuronal apoptosis rate induced by ROT combined with PDSC1-treated astrocyte conditioned medium (PDSC1-ACM) (22.36%) was significantly lower than that induced by A1 cell conditioned medium (44.03%) and ROT combined with A1 cell culture medium (69.43%).

[0425] Table 45 Effects of A2 and A1 cell conditioned medium and their combination with ROT on neuronal apoptosis CON: normal control group; ROT: rotenone; A1CM: A1 astrocyte-conditioned medium; A2CM: A2 astrocyte-conditioned medium; PDSC1-ACM: PDSC1-treated astrocyte-conditioned medium; ** p<0.01, *** p<0.001(vs.CON); # p<0.05, ### p<0.001(vs.ROT); +++ p<0.001(vs.A1CM); @@@ p<0.001(vs.Rot+A1CM); &&&p<0.001 (vs. A1CM); n=5.

[0426] Taken together, these findings suggest that when the neurovascular unit is exposed to mitochondrial mitochondrial enzyme deficiency, inflammatory endothelial cells can injure neurons through a quadruple mechanism: weakening the physiological functions of astrocytes (including their role in maintaining central nervous system homeostasis by clearing excess extracellular Glu and cellular metabolites such as α-synuclein), diminishing the neuroprotective effects of A2 cells, increasing the formation of the neurotoxic phenotype A1, which directly toxics neurons, and increasing the vulnerability of neurons to mitochondrial mitochondrial enzyme deficiency. PDSC1 counteracts the impact of mitochondrial mitochondrial enzyme deficiency by protecting endothelial cells, thereby protecting astrocytes and their neuroprotective functions, thereby disrupting these four mechanisms of neuronal damage.

[0427] Example 10-5. Normal endothelial cells enhance the ability of astrocytes to phagocytose pathological products. A1 cells induced by endothelial cells with insufficient complex enzyme I function lose their phagocytic ability, while A2 cells induced by insufficient complex enzyme I function gain stronger phagocytic ability. PDSC1 can protect endothelial cells and enhance the ability of astrocytes to phagocytose pathological products.

[0428] Based on the findings of Example 10-4, the ability of astrocytes to phagocytose and clear pathological products in the basal state and in the A1 and A2 states was further compared. A fluorescent microsphere phagocytosis assay was used to measure the ability of astrocytes to phagocytose pathological products (including Aβ, whose inability to be cleared leads to amyloid accumulation and neurofibrillary tangle formation, a marker of Alzheimer's disease pathology; and γ-synuclein, whose inability to be cleared leads to deposition, an important pathological mechanism of PD disease and can also lead to dementia). Higher intracellular fluorescence intensity indicates stronger phagocytic ability. The experimental groups included: a normal culture control group, i.e., astrocytes in the basal state (CON); astrocytes treated with 100nM ROT, i.e., the A2 state (ROT / A2); astrocytes treated with normal endothelial cell-conditioned medium (ECM); and astrocytes treated with ROT-induced endothelial cell-conditioned medium, i.e., the A1 state (ROT-ECM / A1).

[0429] The research results are shown in Table 46. The ability of astrocytes in the A2 state induced by 100nM ROT to phagocytose fluorescent microspheres was significantly higher than that of cells in the basal state (CON), while the phagocytic ability of A1 cells conditioned by ROT-induced endothelial cells with complex enzyme I function deficiency (ROT-ECM / A1) was very significantly lower than that of cells in the basal state; unexpectedly, normal endothelial cell conditioned medium (ECM) can also significantly enhance the phagocytic ability of astrocytes, indicating that the active substances released by normal endothelial cells can enhance the phagocytic ability of astrocytes; PDSC1 plus ROT-treated endothelial cell conditioned medium (PDSC1-ROT-ECM) also significantly enhanced the phagocytic ability of astrocytes compared with the normal control group, which is consistent with the result that this conditioned medium promotes the formation of A2 cells.

[0430] Table 46 Effects of endothelial cell conditioned medium and A2 and A1 phenotypes on astrocyte phagocytic ability CON: normal control group; ROT: rotenone; ECM: conditioned medium of normal brain microvascular endothelial cells; ROT-ECM: conditioned medium of brain microvascular endothelial cells treated with rotenone; PDSC1-ROT-ECM: conditioned medium of endothelial cells treated with PDSC1 and ROT; * p<0.05, *** p<0.001(vs.CON); ### p<0.001 (vs. ROT-ECM-induced A1); n=5.

[0431] As can be seen, the research results here, combined with the research results of Examples 10-1 to 10-4, show that endothelial cells with insufficient mitochondrial complex I function not only lose their ability to enhance astrocyte phagocytosis by releasing active substances, but also greatly weaken astrocyte phagocytosis by releasing inflammatory factors, causing astrocytes to transform into the A1 phenotype; PDSC1 can not only inhibit the release of inflammatory factors by endothelial cells with insufficient mitochondrial complex I function, leading to A1 formation, but also maintain their ability to release active substances that promote the A2 phenotype. Obviously, under overall conditions, the reduction in astrocyte phagocytosis may lead to abnormal deposition of γ-synuclein (γ-syn), thereby further deepening the PD disease network; PDSC1 can prevent and control the formation and development of the PD disease network by protecting vascular endothelial cells. In Example 10-6, we confirmed this reasoning.

[0432] Summary and discussion of the research results of Examples 10-1 to 10-5:

[0433] Based on the findings of Examples 10-1 to 10-5, the following conceptual conclusions can be drawn: (1) PD risk factor mitochondrial complex enzyme I deficiency can selectively or preferentially activate the NF-κB pro-inflammatory pathway of vascular endothelial cells and cause them to release inflammatory factors, thereby weakening the beneficial effects of endothelial cells on astrocytes; at the same time, it induces the formation of A1, thereby losing the protective function of astrocytes and acquiring the neurotoxicity of A1 cells, thus greatly widening and deepening the PD disease network initiated by inflammatory endothelial cells, including endothelial cell damage and loss, brain microvascular damage, blood-brain barrier destruction, astrocyte loss, neuroinflammation, abnormal aggregation of α-syn and neuronal damage. In addition, inflammatory endothelial cells upregulate surface adhesion molecules, playing the role of luring wolves (leukocytes) into the room (brain), thus further complicating the PD disease network. It can be seen that protecting the member cells of the neurovascular unit, especially the fragile endothelial cells, is crucial for preventing and treating PD and other neurodegenerative diseases. (2) PDSC1 can prevent and treat the formation and development of the PD disease network caused by the important risk factor of PD (mitochondrial complex enzyme I deficiency) by protecting the member cells of the neurovascular unit; at the same time, PDSC1 can also improve or maintain the physiological functions of vascular endothelial cells, including releasing more NO to improve the state of cerebral vascular tension and the cerebral blood circulation disorders caused by it, promoting the transformation of astrocytes into neuroprotective phenotype A2 cells and the release of neuroprotective active substances, and avoiding the formation of A1 cells, thereby improving the function of the neurovascular unit and its ability to respond to mitochondrial complex enzyme I deficiency.

[0434] In summary, the above research results demonstrate that PDSC1 enhances the ability of astrocytes to clear toxic proteins by protecting endothelial cells and directly protecting astrocytes, thereby directly supporting the medical use of PDSC1 and other effective PDSCs in preventing and treating protein deposition-related diseases including Alzheimer's disease (AD), PD, Lewy body dementia, multiple system atrophy, type I brain iron accumulation neurodegeneration, diffuse Lewy body disease and Lewy body variant of Alzheimer's disease (Cell Biology and Pathophysiology of α-Synuclein. Cold Spring Harb Perspect Med. 2018; 8(3): a024091.).

[0435] In addition, the reduction in NO production caused by endothelial dysfunction is associated with cardiovascular diseases such as hypertension and atherosclerosis (J Pharmacol Sci. 2015 Oct; 129 (2): 83-94.), and will also lose the protective function of the neurovascular unit (NVU), thereby promoting cognitive decline in the elderly (Stroke. 2023; 54 (3): 686-696.). Therefore, our research results also support the medical use of PDSC1 and other effective compositions in preventing and treating cardiovascular diseases such as hypertension and atherosclerosis, age-related cognitive impairment, and other diseases related to vascular endothelial lesions. According to the research results of the existing examples, it can be predicted that in the brain of PD rats induced by ROT, the vicious cycle of mutual damage between the member cells of the neurovascular unit initiated by inflammatory endothelial cells will eventually lead to blood-brain barrier destruction, microvascular and endothelial cell damage, and loss of surrounding astrocytes. PDSC1 can protect the blood-brain barrier, microvascular, endothelial cells, and their surrounding astrocytes. In Example 10-6, we verified this prediction.

[0436] Example 10-6. The rotenone (ROT)-induced PD model in rats also has a chain pathological reaction of neurovascular unit triggered by inflammatory endothelial cells. PDSC1 can prevent ROT from activating NF-κB and subsequent pathological changes and damage to the member cells of the neurovascular unit; the effective composition starts by protecting endothelial cells to fight against the formation and development of the PD disease network involving endothelial cells, astrocytes and neurons.

[0437] Here, the conceptual conclusions obtained from the research findings of Examples 10-1 to 10-5 were verified using a ROT-induced PD rat model (the role of inflammatory endothelial cells in initiating a vicious chain reaction between member cells of the neurovascular unit in the formation and development of the PD disease network; and that PDSC1 can prevent and treat the formation and development of the PD disease network caused by insufficient mitochondrial complex I function, a key risk factor for PD, by protecting vascular endothelial cells). To reveal the essential differences between the pharmacological effects of PDSC1 and the dopamine replacement therapy L-DOPA, the pharmacological effects of certain indicators of PDSC1 (40 mg / kg / day, the effective dose previously discovered) and L-DOPA (Madopar, equivalent to 7 times the initial dose for PD patients) were also compared here. To determine whether and in what order NF-κB p65 activation (marker p-p65), the emergence of A1 cells (marker C3d), ​​microglial activation (marker iba1), abnormal deposition of α-syn (soluble and insoluble non-phosphorylated and phosphorylated forms; α-syn phosphorylation indicates the spread of pathological proteins within the brain), and endothelial cell and dopamine neuron (marker TH) death occur in the brains of PD rats, we performed observations before (D0) and on the second (D2), tenth (D10), and fifteenth (D15) days after ROT administration. Western blotting (WB, striatum only) and immunohistochemistry were used to assess these parameters. In addition, blood-brain barrier and cerebral microvascular damage were also assessed in samples taken on day 15. Fluorescently labeled proteins were delivered to the cerebral vascular network through cardiac perfusion to detect damage to the blood-brain barrier. EBA and GFAP were used as markers of endothelial cells and astrocytes, respectively, and fluorescent immunostaining and double staining were used to observe the morphology of microvessels and their relationship with surrounding astrocytes.

[0438] The results of WB analysis showed (Figure 2, Table 47 and Table 48) that compared with before ROT administration (D0), NF-κB was significantly activated in the striatum and A1 cells began to appear on the second day (D2) of ROT administration, while other indicators did not show significant changes in the striatum and substantia nigra pars compacta; on the 10th day (D10), NF-κB activation (p-p65 upregulated to a peak) and the number of A1 cells reached a peak (C3d upregulated to a peak), microglia activation (iba1 upregulated), and the levels of soluble and insoluble non-phosphorylated and phosphorylated α-synuclein increased to a peak. Consistently, immunohistochemistry results (Figure 3) showed that p65 staining in the striatum revealed blood vessels starting on day 2. Striatal astrocytes showed separation of cell bodies and processes. In particular, the vascular structures formed by the astrocyte end plates were structurally incomplete compared with those in normal animals (D0), and the surrounding GFAP-positive fibers disappeared in large numbers. Moreover, these pathological changes in astrocytes intensified with time. No morphological changes in microglia were observed at this time, and no iNOS expression was observed in brain vessels. By day 10, microglia exhibited an amoebic state, indicating activation (Figure 2, A). Inflammatory endothelial cells expressed iNOS staining (Figure 3, C). TH levels in the dorsolateral striatum (a brain region that primarily receives projections from the limb representation area of ​​the sensorimotor cortex and plays an important role in normal motor function, motor skill learning, and habit formation) decreased significantly (Figure 3, D). However, no significant changes were observed in the substantia nigra pars compacta. On day 15, TH levels in the striatum decreased further, and TH levels in dopamine nerve fibers in the substantia nigra pars compacta were almost completely lost. Thus, the sequence of endothelial NF-κB p65 activation, the appearance of A1 cells, the spread and abnormal accumulation of pathological α-syn in the striatum and substantia nigra, and dopamine nerve damage in the ROT-induced PD rat model is highly consistent with the findings in the cell model. It should also be noted that microglial activation occurs after endothelial cell NF-κB activation and the appearance of A1 cells. This order is consistent with the result that 100nM only activates endothelial cell NF-κB without affecting microglia and other cells in the neurovascular unit. This once again shows that in the development and progression of ROT-induced PD, inflammatory factors released by endothelial cells are the primary driving force for the transformation of astrocytes to the A1 phenotype. According to literature reports, subsequent pathologically activated microglia will also join the ranks of promoting A1 transformation.

[0439] Table 47 The pathological progression of neurovascular unit and the role of PDSC1 in the occurrence and development of ROT-induced PD rat model * p<0.05, ** p<0.01, *** p<0.001 (vs. normal control group); ###p<0.001 (vs. ROT model group on day 15); n=3.

[0440] Table 48 The development and progression of α-synuclein pathology in ROT-induced PD rat model and the role of PDSC1 ** p<0.01, *** p<0.001 (vs. normal control group); ### p<0.001 (vs. ROT model group on day 15); n=3.

[0441] Consistent with the pharmacological effects observed in cell models, PDSC1 inhibited chronic ROT-induced endothelial cell NF-κB activation, astrocyte conversion to the A1 phenotype, microglial activation, and the spread and abnormal aggregation of toxic α-syn. It also protected striatal and substantia nigra dopamine neuronal pathways and cerebral vasculature. Specifically, PDSC1 administered 45 minutes before each ROT dose completely prevented ROT-induced NF-κB activation, as indicated by increased p-p65 and p65 levels, the emergence of A1 cells, as indicated by increased C3d levels, and microglial activation, as indicated by increased iba1 levels (Figure 2, Tables 47 and 48). PDSC1 also completely antagonized ROT-induced increases in soluble phosphorylated and non-phospho-α-syn levels in the striatum, and significantly antagonized increases in both insoluble and non-phospho-α-syn levels. Immunohistochemical results also demonstrated that PDSC1 almost completely antagonized ROT-induced phosphorylated α-syn aggregation in the striatum and substantia nigra pars compacta (Figure 2, B). It can be seen that PDSC1 can comprehensively counteract the α-syn pathological process induced by ROT, including the spread and abnormal aggregation of toxic α-syn. This proves that the PDSC1 protection found in the previous examples can be converted into a drug effect on animal models by improving the clearance of toxic proteins through endothelial cells and astrocytes. Consistent with the above-mentioned pharmacological effects, PDSC1 can almost completely counteract ROT-induced loss of striatal dopamine nerve endings (D in Figure 3) and loss of dopamine nerve fibers in the substantia nigra (E in Figure 3). L-DOPA has no obvious neuroprotective effect, but its combination with PDSC1 does not negatively affect the efficacy of PDSC1. This powerful protective effect stems from the direct protective effect of PDSC1 on the member cells of the neurovascular unit and its role in preventing and treating inflammatory endothelial cells that trigger damage to the member cells of the neurovascular unit, leading to the occurrence and development of the PD disease network.

[0442] Figures 4 and 5 further demonstrate the vascular damage and surrounding astrocyte lesions in the striatum and substantia nigra of the animals in the model control group on day 15, as well as the protective effect of PDSC1. In the striatum, the vascular structure of normal (naive) animals was intact, with astrocyte endplates tightly adhered to the vascular wall, forming a complete structure (Figure 4A and B). However, in ROT model rats, a large number of astrocytes around the blood vessels were lost, with no close contact between astrocytes and the vascular wall, and the vascular structure was fragmented (Figure 4A and 4B). This phenomenon supports the conclusion obtained from the cell model that inflammatory endothelial cells exacerbate the vulnerability of astrocytes to ROT. L-DOPA had no significant protective effect on astrocytes, nor did it protect blood vessels or the tight junctions between blood vessels and glial cells. In the PDSC1 and L-DOPA combination groups, astrocytes were tightly attached to the vascular wall, and the glial-vascular unit structure was intact, almost identical to that of normal rats, indicating that PDSC1 can almost completely protect against ROT-induced toxicity to the neurovascular unit, and when combined with L-DOPA, L-DOPA does not negatively affect the protective effect of PDSC1. Consistently, as shown in Figure 5, a large amount of fluorescently labeled protein leakage occurred in the striatum (Figure 5A) and the pars compacta (SNc) and ventral part (VTA) of the substantia nigra (Figure 5B) of the PD model animals induced by ROT, indicating that the brain microvessels and blood-brain barrier were severely damaged; L-DOPA had a certain protective effect on the blood-brain barrier of the substantia nigra, but no obvious protective effect was seen in the striatum. However, PDSC1 and the combination of PDSC1 and L-DOPA had very significant protective effects on the microvessels and blood-brain barrier of the striatum and the pars compacta and ventral part of the substantia nigra. It can be seen that PDSC1 has a very strong effect of protecting vascular endothelial cells, astrocytes and the blood-brain barrier against ROT toxicity, and this protective effect is not affected by L-DOPA. This strongly supports the medical use of effective PDSC combined with L-DOPA to treat PD, especially in the middle and late stages of PD, which can make up for the inability of L-DOPA to slow disease progression.

[0443] Conclusion and Discussion:

[0444] The results of the ROT-induced PD rat model study confirmed the conceptual conclusions obtained from the findings of Examples 10-1 to 10-5, namely: mitochondrial complex enzyme I deficiency can selectively or preferentially activate the NF-κB proinflammatory pathway in vascular endothelial cells and cause them to release inflammatory factors, thereby weakening the beneficial effects of endothelial cells on astrocytes and inducing the formation of type A1 astrocytes. Subsequent pathological activation of microglia will also join the ranks of promoting the transformation of type A1 cells; A1 cells not only lose their original physiological functions such as clearing toxic proteins and release toxic substances, but also greatly widen and deepen the PD disease network initiated by inflammatory endothelial cells, including endothelial cell damage and loss, brain microvascular damage, blood-brain barrier disruption, astrocyte pathology and loss, microglial activation, abnormal aggregation of α-syn and damage to the nigrostriatal dopamine pathway. In addition, upregulation of surface adhesion molecules by inflammatory endothelial cells can attract wolves (leukocytes) into the room (brain), further complicating the PD disease network. Endothelial cell dysfunction and blood-brain barrier damage are common in cerebrovascular diseases including neurodegenerative diseases such as Alzheimer's disease and cerebral stroke. Therefore, our research results show that protecting brain vascular endothelial cells can prevent the damage process of the neurovascular unit initiated by the deficiency of complex enzyme I caused by environmental toxins, which has important therapeutic value for the prevention and treatment of PD, and is also of great value for the prevention and treatment of other neurodegenerative diseases and cerebrovascular diseases. It can be seen that compared with the publicly disclosed drug targets for the development and prevention of neurodegenerative diseases such as PD, such as neurons, glial cells, or inflammatory reactions and α-syn toxicity, the neurovascular unit as a whole, including endothelial cells, is more scientific, feasible and efficient, and these three properties have been verified by the efficacy of PDSC1 and other effective compositions.

[0445] PDSC1 can protect endothelial cells from initiating the PD disease network caused by synaptophysin I deficiency, a risk factor for PD. This can avert a series of subsequent pathological events, including infiltration of peripheral immune cells across the blood-brain barrier into brain tissue, formation of type A1 cells, loss of astrocyte function, pathological microglial activation, neuroinflammation, pathological spread and deposition of α-synuclein, damage to the nigrostriatal dopamine pathway, severe loss of endothelial cells and peripheral astrocytes, and severe damage to the blood-brain barrier. PDSC1 also enhances the altruistic physiological functions of endothelial cells and astrocytes toward other members of the neurovascular unit, thereby improving the overall neurovascular unit's ability to cope with synaptophysin I deficiency. This can potentially correct early pathological changes in PD and restore affected motor function and neuropsychiatric behaviors. PDSC1 also directly protects other members of the neurovascular unit against the cytotoxicity caused by synaptophysin I deficiency, thereby slowing or even interrupting the vicious cycle between different NVU cell components during PD development, thereby delaying or even halting disease progression. These pharmacological effects reveal the pharmacological effects of the superior / effective ginsenoside composition, including PDSC1, in systematically preventing and treating the formation and deep progression of PD disease networks with its unique mechanism of action, thereby demonstrating the medical use of the superior / effective ginsenoside composition in preventing and treating PD from the root cause in terms of therapeutic principles. Therefore, it can break the long-standing deadlock in the treatment of PD at home and abroad that only treats the symptoms but not the root cause (existing drugs all aim to relieve symptoms, there are no drugs to delay disease progression, and there are no drugs to prevent the occurrence of the disease).In particular, in addition to being involved in PD, α-syn pathology is also involved in the initiation and progression of Lewy body dementia (DLB), multiple system atrophy (MSA), type I brain iron accumulation neurodegeneration, diffuse Lewy body disease, Lewy body variant of Alzheimer's disease, progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) (Cold Spring Harb Perspect Med. 2018; 8(3):a024091. Alzheimer Dis Assoc Disord. 2020; 34(3):220-224. Nat Rev Dis Primers. 2022; 8(1):56.), which are collectively referred to as synucleinopathies; cerebral microvascular lesions and endothelial cell dysfunction (Neuron. 2017; 96(1):17-42; Nat Rev Neurol. 2022; 18(10):597-612; Nat Neurosci. 2022; 25(8): 1034-1048.), astrocyte dysfunction or acquired toxicity (Neuropathology. 2014; 34(6): 555-70.), and neuroinflammation (Front Immunol. 2023: 14: 1214677.) are also involved in the occurrence and development of these neurodegenerative diseases. Therefore, our research results strongly support the medical use of PDSC superior / effective compositions in preventing and treating the above-mentioned synucleinopathies.

[0446] It should be noted that, based on the common mechanisms of multiple diseases, our research results also strongly support the medical use of PDSC1 and other effective compounds in preventing and treating other neurodegenerative diseases, neurodestructive diseases and retinal diseases. First, the role of cerebral microvessels in diseases including vascular dementia and Alzheimer's disease (AD), chorea (HD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) is increasingly recognized (Neuron. 2017; 96(1): 17-42; Nat Rev Neurol. 2022; 18(10): 597-612; Nat Neurosci. 2022; 25(8): 1034-1048.). For example, recent studies have shown that damage to the blood-brain barrier (BBB) ​​is an early biomarker of cognitive dysfunction, including AD; various cerebrovascular risk factors (such as hypercholesterolemia, hypertension, etc.) and injury events (such as long-term hypoperfusion, ischemic or hemorrhagic stroke, transient ischemic attack, and stroke recovery) can cause neurodegeneration or severe damage by damaging the neurovascular unit and BBB, thereby leading to brain dysfunction or even disability; endothelial cell dysfunction and BBB destruction are also important causes of retinal diseases (including diabetic retinopathy, glaucoma, macular edema, and age-related macular degeneration) (Antioxidants (Basel). 2020; 9(8):761. Fluids Barriers CNS. 2018; 15(1):24.). Second, amyloid deposition (peptides assembled into amyloid fibrils) is considered a core pathological hallmark of another age-related disease, such as amyloid β (Aβ), phosphorylated tau (tau), and apolipoprotein E4 (APOE4) in AD, islet amyloid polypeptide (IAPP, amylin) in type 2 diabetes, and α-synuclein (α-syn) in PD. Furthermore, one protein can accelerate the deposition of another. For example, soluble IAPP can cross the blood-brain barrier and, when coexisting with soluble Aβ or α-syn, accelerates amyloid formation. This is a key reason why the incidence of AD and PD in type 2 diabetic patients is much higher than in non-diabetic individuals. A single toxic protein is associated with multiple diseases. As previously mentioned, α-syn pathology is implicated in retinal degeneration, in addition to PD and other neurodegenerative diseases (Prog Retin Eye Res. 2020:74:100771). PDSC1 can indirectly and directly protect astrocytes and enhance their ability to clear various toxic proteins. Third, neuroinflammation is another common pathological event in various neurodegenerative diseases including PD and AD (Metab Brain Dis. 2021; 36(7): 1591-1626. Neurosci Biobehav Rev. 2023: 144: 104961.).A large number of drug developments have been conducted for these pathological events, such as Aβ antibodies and α-syn antibodies targeting toxic proteins, but most of them have ended in failure in clinical trials. Therefore, targeting neuroinflammation and the upstream of these toxic proteins is crucial for the prevention and treatment of neurodegenerative diseases. The results of Examples 9 and 10 show that brain microvascular endothelial cell damage and the inflammatory factors released and subsequent A1 cell formation are key upstream events in mitochondrial complex enzyme I deficiency-induced BBB destruction, neuroinflammation, α-syn deposition and neurodegeneration. PDSC1 can protect endothelial cells, astrocytes and their physiological functions, including the clearance of toxic proteins, microglia and neurons, thereby preventing the formation and deep progression of disease networks.

[0447] In addition, endothelial dysfunction and the resulting decrease in NO levels are associated with cardiovascular diseases such as hypertension and atherosclerosis (J Pharmacol Sci. 2015; 129(2): 83-94.). Endothelial dysfunction and decreased NO levels also weaken or lose its protective function for the NVU and promote the development of cognitive impairment associated with normal aging (Stroke. 2023; 54(3): 686-696.). Therefore, the role of PDSC1 in protecting endothelial cells and increasing their NO secretion levels also supports the medical and health care uses of ginsenosides and effective compositions for preventing and treating cardiovascular diseases such as hypertension and atherosclerosis and slowing down the aging of brain functions, including cognitive function.

[0448] Example 11. Pharmacological study on the superior composition PDSC1 in protecting parvalbumin-positive interneurons (PV-Ins).

[0449] To further reveal the broad neuroprotective effects of PDSC1 and its widespread medical applications in preventing and treating neuropsychiatric disorders, we investigated parvalbumin-expressing interneurons (PV-INs), a vulnerable neurodegenerative disorder, in the striatum of PD rats induced by the complex enzyme I inhibitor ROT, and examined the protective effects of PDSC1 on these neurons. PV-INs are important inhibitory interneurons that use GABA as a transmitter. They are crucial for maintaining the balance between the inhibitory neurotransmitter GABA and the excitatory neurotransmitter glutamate (Glu), and also regulate the release of other neurotransmitters. Therefore, they are deeply involved in the physiological activities of the cerebral cortex and striatum. PV-INs are particularly susceptible to environmental risks such as mitochondrial dysfunction or insufficient energy production (ATP), high extracellular Glu levels, oxidative stress, inflammation, and social stress. Therefore, PV-IN dysfunction plays an important role in many neuropsychiatric diseases, including neurodegenerative diseases such as AD and Lewy body dementia, mood and mental disorders (bipolar disorder, schizophrenia, etc.), excitatory diseases such as epilepsy, and neurodevelopmental disorders (such as Coeliac disease, ADHD, and autism) (Neuropsychopharmacology.2023; 48(2):391-401. Neuropsychopharmacology.2021; 46(2):279-287. Prog Brain Res.2016:226:81-126. Front Psychiatry.2022:13:913550.) and stress-induced mental disorders (Rev Neurosci.2016; 27(4):397-409.). Within the striatum, PV-INs exert a powerful inhibitory control effect, thereby maintaining the firing rate of medium spiny neurons (SPNs) in the efferent nerves at a low physiological level. Therefore, insufficient function of striatal PV-INs can directly lead to movement disorders, and their insufficient function and the accompanying Glu hyperexcitability are closely related to drug addiction (Front Psychiatry. 2021:12:679960). PV+ interneurons have been considered an important target for future treatment of brain diseases (Science. 2014Aug 1;345(6196):1255263.).

[0450] Methods: Using the striatal samples from Example 10-6, immunohistochemistry and immunofluorescence were used to assess the density of PV-positive neurons and fibers in the striatum to clarify the function and survival of PV-INs. The level of PV immunostaining is positively correlated with the functional status of PV-INs. Loss of staining does not necessarily mean neuronal loss, but at least indicates severe functional impairment or even loss. Serial coronal sections (40 μm) were taken from the striatum (27 consecutive sections starting at 1.7 mm from bregma) using conventional methods, and brain slices were collected for semi-quantitative analysis. Briefly, the brain region containing the striatum was divided into three sections (9 sections per section) for each animal, and one section from each section was analyzed for PV-positive particle density. The average of the three sections was used as the data for one animal. Semi-quantitative analysis was performed in four regions of the striatum: the dorsal lateral (DL), dorsal media (DM), ventral lateral (VL), and ventral media (VM).

[0451] As shown in Table 49, immunohistochemical staining showed that compared with normal animals, the PD rat model group had a decrease in PV-positive cell bodies in all four regions of the striatum, especially immunofluorescence staining showed an almost complete loss of PV-positive fibers (Figure 6); compared with the model group, L-DOPA increased PV-positive particles in DL, DM, VL and VM, but no selectivity difference was observed; PDSC1 and PDSC1 combined with L-DOPA significantly increased PV-positive particles in DL, DM, VL and VM ( ## The results showed that ROT-induced PD rats showed widespread severe degeneration of PV-IN function in the striatum, revealing the pathological role of striatal PV-IN function degeneration in the development and expression of neuropsychiatric states of PD. PDSCs can protect striatal GABA interneurons, represented by PV-INs, against the damage caused by insufficient or absent complex enzyme I function, further clarifying the broad protective effect of PDSC1 on various members of the neurovascular unit, including PV-INs.

[0452] Table 49 ROT-induced reduction of PV-positive GABA interneurons in the striatum of PD rats and the protective effect of PDSC1 ROT: rotenone; L-DOPA: levodopa; PDSC1: panaxadiol saponin composition 1; ** p<0.01 (vs. normal control group); ## p<0.01 (vs. ROT model group); n=5.

[0453] Summary and discussion:

[0454] Based on the physiological functions of PV-INs, degeneration of striatal PV-IN function in PD can directly participate in or even lead to hyperexcitability of spiny neurons (SPNs), thereby triggering motor symptoms. It can also lead to or aggravate striatal Glu hyperexcitability and other neurotransmitter level disorders, aggravating motor symptoms, triggering neuropsychiatric symptoms, and accelerating disease progression. Therefore, the pharmacological effect of PDSC1 in protecting striatal GABA interneurons, represented by PV-INs, from the harmful effects of complex enzyme deficiency / deficiency predicts that PDSC1 can maintain and repair the balance of neural excitability and inhibition in the striatum and other disease-related brain regions of PD patients, and has a breakthrough efficacy in preventing and treating PD, namely: it can simultaneously alleviate motor symptoms and central non-motor symptoms (including various mental disorders and cognitive impairments) and delay the progression of PD. It can also prevent and treat the medical use of levodopa (L-DOPA) to treat dyskinesias and neuropsychiatric disorders including delusions and hallucinations.

[0455] In particular, the role of PDSC1 in enhancing PV-INs' response to complex enzyme I deficiency without dysfunction reflects the broad protective role of PDSC1 in protecting PV-INs against other environmental perturbations and its medical and healthcare applications in preventing and treating brain diseases associated with PV-IN dysfunction, including: neurodegenerative diseases such as AD, Lewy body dementia and frontotemporal dementia, cognitive decline associated with natural aging, mood and behavioral disorders (such as schizophrenia and bipolar disorder), epilepsy formation and seizures, neurodevelopmental disorders (such as Tourette syndrome, ADHD, autism), and stress-induced psychological disorders and post-traumatic stress disorder, as well as drug addiction.

[0456] Example 12. Protecting energy metabolism and redox homeostasis and avoiding neuroinflammation are important mechanisms by which the potent composition exerts its broad brain protective effects.

[0457] Rotenone (ROT) selectively inhibits mitochondrial respiratory chain complex I, thereby preventing electrons (primarily in the form of NADH) generated by the tricarboxylic acid (TCA) cycle from entering the oxidative respiratory chain, thereby inhibiting the oxidative phosphorylation pathway, ultimately leading to mitochondrial dysfunction including decreased adenosine triphosphate (ATP) levels, redox imbalance, oxidative stress damage, and subsequent inflammatory response. This biochemical pathology is an important upstream mechanism for the development and progression of PD, and currently there is no drug that can prevent or mitigate this upstream pathogenic event. To date, PD patients continue to progress despite receiving multiple drug treatments, including the gold standard drug L-DOPA. Based on the research findings in the previous examples, the applicant believes that low concentrations of ROT can preferentially disrupt endothelial cell energy metabolism and redox homeostasis, while other member cells of the neurovascular unit, especially astrocytes, have a strong ability to maintain energy metabolism and redox homeostasis. Therefore, endothelial cells are most vulnerable to ROT; similarly, PDSC1 can enhance the cell's ability to maintain energy metabolism and redox homeostasis, thereby protecting endothelial cells from the toxicity of ROT. Based on this, the following three confirmatory studies were carried out. The results can not only clarify the biochemical essence of endothelial cell vulnerability to complex enzyme I deficiency and the protective effect of PDSC1, but also further reveal the common mechanism of action of PDSC1 and other effective combinations in preventing and treating neurodegenerative diseases and other mitochondrial dysfunction-related diseases.

[0458] Example 12-1. Comparative study of the effects of ROT on energy metabolism and redox homeostasis in endothelial cells and astrocytes / ROT preferentially reduces ATP and NAD in endothelial cells + levels, disrupting redox balance and damaging mitochondria; astrocytes increase NAD + Levels and NAD + / NADH ratio to effectively cope with insufficient mitochondrial complex I function and maintain energy metabolism, redox balance and mitochondrial function.

[0459] Brain microvascular endothelial cells (BMEC) and astrocytes (ASC) were routinely cultured and treated with 100nM ROT for 36h to examine changes in cellular energy metabolism, oxidative stress and central carbon metabolism, and to analyze the role of PDSC1 in metabolic regulation. Various indicators were measured using conventional methods. As shown in Table 50, after 36h of treatment with 100nM ROT, the intracellular ATP level of BMEC decreased by 50%, ADP accumulated in large quantities, and the ATP / ADP ratio decreased by 75% (p<0.001). These data indicate that the oxidative phosphorylation activity of BMEC mitochondria was severely damaged. Accordingly, the level of NADH (reduced coenzyme I), which provides electron donors for the oxidative phosphorylation pathway, increased to 325% (p<0.001), while NAD +(nicotinamide adenine dinucleotide, also known as oxidized coenzyme I) showed a downward trend, leading to NAD + The / NADH ratio decreased to 21% (p<0.001), which will lead to further energy metabolism disorders. In sharp contrast, although ASC's oxidative phosphorylation was also significantly reduced, the extent was much lower than that of BMEC. The ATP level and ATP / ADP ratio decreased by 29% and 35%, respectively, which were significantly lower than the 50% and 75% of endothelial cells. It can be seen that the ability of ASC's mitochondrial oxidative phosphorylation activity to resist the deficiency or loss of complex enzyme I function is much stronger than that of BMEC. In particular, ROT treatment did not reduce but significantly increased ASC's NAD + level (p<0.01), while the NADH level remained basically unchanged, making NAD + / NADH ratio increased to 156%. It should be noted that NAD + As a coenzyme in redox reactions, it is the center of energy metabolism and is crucial for maintaining energy metabolism homeostasis. + The availability of NAD is a key determinant of the rate of NADH and pyruvate flow into mitochondria and, therefore, of glycolysis, or the rate of glycolysis. + / NADH ratio. Since the TCA cycle and electron transporter channels require NAD + and NADH, thus requiring an optimal NAD + / NADH ratio to achieve efficient mitochondrial metabolism. Scavenging cytoplasmic NAD + This blocks glycolysis and leads to cell death. + Its absence leads to mitochondrial dysfunction, decreased energy production and accumulation of ROS, resulting in high oxidative stress. + Many other critical cellular functions, including DNA repair, chromatin remodeling, and cellular senescence, can be directly or indirectly affected through sirtuins, CD38, and poly (ADP-ribose) synthase (PARP).

[0460] Table 50 The plasticity of endothelial cell energy metabolism in response to mitochondrial complex enzyme I deficiency is weaker than that of astrocytes ROT: rotenone; ATP: adenosine triphosphate; ADP: adenosine diphosphate; ATP / ADP: ratio of adenosine triphosphate to adenosine diphosphate; NAD + : oxidized nicotinamide adenine dinucleotide; NADH: reduced nicotinamide adenine dinucleotide; NAD + / NADH: ratio of oxidized nicotinamide adenine dinucleotide to reduced nicotinamide adenine dinucleotide; ***p<0.001 (vs. normal control group); n=5.

[0461] In summary, rotenone (ROT) induces NAD + Levels and NAD + A severe decrease in the NAD / NADH ratio limits its ability to respond to the reduced ATP production and harmful reactions caused by ROT inhibition of complex enzyme I by activating cellular self-rescue mechanisms (such as glycolysis, TCA cycle, and oxidative phosphorylation activities), leading to new energy metabolism disorders and other NAD-dependent + The disorder of biochemical processes eventually leads to mitochondrial dysfunction, energy depletion, ROS accumulation and oxidative stress. + Levels and NAD + An increased NADH / NADH ratio helps astrocytes cope with mitochondrial complex I deficiency by enhancing glycolysis, TCA cycle, and oxidative phosphorylation activities. Therefore, astrocytes with complex enzyme I deficiency can maintain intracellular ATP levels and mitochondrial functional homeostasis, thereby avoiding ROS accumulation and high oxidative stress and the harmful reactions they produce.

[0462] Based on this, we further investigated the effects of 100 nM ROT exposure on the oxidative stress status of endothelial cells and astrocytes. The indices examined included reduced coenzyme II (NADPH), glutathione (GSH) and its oxidized form NADP. + The levels of NADPH and GSH, their total amount and the ratio of reduced to oxidized forms, as well as the levels of reactive oxygen species (ROS), an indicator of oxidative stress, and mitochondrial membrane potential (MMP), an indicator of mitochondrial damage, were analyzed. NADPH and GSH are two of the most important antioxidants in the body, and are crucial for reducing intracellular ROS and preventing oxidative stress damage. When GSH scavenges ROS and is oxidized to GSSG, NADPH is required as an electron donor to be reduced to GSH. Therefore, the ratios of GSH / GSSG and NADPH / NADP are similar. + The ratio and ROS level can directly reflect the cellular redox state and oxidative stress.

[0463] The results are shown in Table 51. Exposure of BMEC to 100 nM ROT for 36 hours significantly reduced intracellular GSH levels to 59%, accompanied by a nearly 6-fold increase in GSSG levels and a 91% decrease in the GSH / GSSG ratio. There was also a trend toward an increase in total glutathione (GSH+GSSG), indicating that the reduction in GSH levels was not related to synthesis but was due to the impairment of the process of GSSG reduction to GSH. + The balance of NADPH and (NADPH+NADP +) or NADPH / NADP + The ratios were significantly reduced, but NADP + The level has not decreased but has increased. The above results indicate two points: first, NADPH production is reduced, and second, NADP + Cannot be restored to NADPH in time, thus causing NADPH / NAPD + As a direct consequence of the severe decrease in these two ratios, ROS levels increased significantly, while MMP decreased significantly. + The reduction in regeneration led to a decrease in NADPH levels in endothelial cells, which in turn led to GSSG accumulation and decreased GSH levels, increased ROS levels, and mitochondrial damage. Consistent with the results of energy metabolism, ROT treatment under the same conditions did not significantly affect these parameters of astrocytes, and the GSH / GSSG ratio tended to increase, indicating that astrocytes have the ability to resist the deficiency of mitochondrial complex enzyme I function, which leads to NADPH production and NADP + Reduction in regeneration, thus maintaining NADPH and NADPH / NADP + The homeostasis of the ratio can maintain the homeostasis of GSH and GSH / GSSG ratio, thus avoiding redox imbalance and oxidative stress damage.

[0464] Table 51 The plasticity of endothelial cell redox balance in response to mitochondrial complex enzyme I deficiency is weaker than that of astrocytes ROT: rotenone; GSH: reduced glutathione; GSSG: oxidized glutathione; GSH+GSSG: the sum of reduced and oxidized glutathione; GSH / GSSG: the ratio of reduced to oxidized glutathione; NADPH: reduced nicotinamide adenine dinucleotide phosphate; NADP + : Oxidized nicotinamide adenine dinucleotide phosphate; NADPH+NADP + : Total nicotinamide adenine dinucleotide phosphate; NADPH / NADP + : ratio of reduced to oxidized nicotinamide adenine dinucleotide phosphate; ROS: reactive oxygen species; MMP: mitochondrial membrane potential; ** p<0.01, *** p<0.001 (vs. CON); n=5.

[0465] Summary and discussion: The above research results show that ROT preferentially reduces ATP and NAD in endothelial cells. + level, but increases NADH levels, leading to NAD + / NADH ratio is seriously unbalanced, NADPH / NADP+ The redox balance of GSH / GSSG is severely disrupted, and mitochondria are damaged. Astrocytes increase NAD + Levels and NAD + / NADH ratio to effectively cope with the insufficient function of mitochondrial complex enzyme I and maintain energy metabolism in the state of insufficient complex enzyme I function, NADPH / NADP + This profoundly explains the IC of ROT on endothelial cells. 50 The IC value for astrocytes is about 100 nM. 50 The scientific reason for the value of about 2000nM. Therefore, it is necessary to improve the metabolic plasticity of neurovascular unit member cells, especially endothelial cells, in response to insufficient or missing mitochondrial complex enzyme I function, and maintain ATP and NAD + , NADPH and NADPH+NADP + The study of GSH levels is crucial for preventing and treating the development and progression of PD, offering a novel approach to the search and discovery of effective anti-PD drugs. Based on this, the applicants believe that PDSC1 and other potent compositions enhance this response capacity, thereby eliminating the vulnerability of endothelial cells to complexase I deficiency or loss, enabling them to withstand complexase I deficiency without developing disease, similar to astrocytes. Therefore, we designed Example 12-2 to further validate this hypothesis.

[0466] Example 12-2. PDSC1 can maintain ATP and NAD in endothelial cells with low or deficient mitochondrial complex I function + levels, redox homeostasis, mitochondrial function and prevent oxidative stress damage.

[0467] We investigated whether PDSC1 could enhance the plasticity of endothelial cells in response to the inhibition of mitochondrial complex I by rotenone (ROT).

[0468] Table 52 PDSC1 enhances endothelial cell metabolic and redox balance plasticity in response to mitochondrial complex I deficiency ROT: rotenone; PDSC1: panaxadiol saponin composition; ATP: adenosine triphosphate; ADP: adenosine diphosphate; ATP / ADP: ratio of adenosine triphosphate to adenosine diphosphate; NADH: reduced nicotinamide adenine dinucleotide; NAD + : Oxidized nicotinamide adenine dinucleotide; NADH / NAD + : ratio of reduced nicotinamide adenine dinucleotide to oxidized nicotinamide adenine dinucleotide; NADH+NAD +:...

Claims

1. A ginsenoside composition, characterized in that: The ginsenoside composition comprises a functional unit 1 and a functional unit 2, wherein the functional unit 1 comprises Rb1 and Rd, and the functional unit 2 comprises Rc and Rb3; The mass ratio of the functional unit 1 to the functional unit 2 is 0.66 to 1.

92.

2. The ginsenoside composition according to claim 1, characterized in that The ginsenoside composition is a ginsenoside composition of ginsenoside diols; Preferably, in the ginsenoside composition, the mass ratio of Rb1 to Rd is 0.79-2.08, the mass ratio of Rb1 to Rc is 0.67-2.17, the mass ratio of Rb1 to Rb3 is 0.82-2.76, and the mass ratio of Rc to Rb3 is 0.79-2.11; Preferably, the mass ratio of Rb1, Rc, Rb3 and Rd is (1.953-2.387): (0.9-1.1): (1.143-1.397): (1.908-2.332), for example, about 2.17: about 1.00: about 1.27: about 2.12; Preferably, the mass ratio of Rb1, Rc, Rb3 and Rd is (1.242-1.518): (0.9-1.1): (0.567-0.693): (1.566-1.914), for example, about 1.38: about 1.00: about 0.63: about 1.74; Preferably, the mass ratio of Rb1, Rc, Rb3 and Rd is (0.9-1.1): (0.9-1.1): (0.423-0.517): (0.576-0.704), for example, about 1.00: about 1.00: about 0.47: about 0.64; Preferably, the mass ratio of Rb1, Rc, Rb3 and Rd is (0.684-0.836): (0.9-1.1): (0.612-0.748): (0.468-0.572), for example, about 0.76: about 1.00: about 0.68: about 0.52; Preferably, the mass ratio of Rb1, Rc, Rb3 and Rd is (0.675-0.825): (0.9-1.1): (0.504-0.616): (0.594-0.726), for example, about 0.75: about 1.00: about 0.56: about 0.66; Preferably, the mass ratio of Rb1, Rc, Rb3 and Rd is (1.251-1.529): (0.9-1.1): (0.981-1.199): (0.819-1.001), for example, about 1.39: about 1.00: about 1.09: about 0.91; Preferably, the mass ratio of Rb1, Rc, Rb3 and Rd is (0.909-1.111): (0.9-1.1): (0.981-1.199): (0.657-0.803), for example, about 1.01: about 1.00: about 1.09: about 0.73; Preferably, the ginsenoside composition further comprises Rb2; Preferably, based on the mass of the ginsenoside composition being 100%, the mass percentage of Rb1, Rc, Rb2, Rb3 and Rd is greater than about 85%, wherein the mass percentage of Rb2 is 0.1% to 16%.

3. The ginsenoside composition according to claim 1, characterized in that The ginsenoside composition is a holographic ginsenoside composition or a total ginsenoside composition; Preferably, the holographic ginsenoside composition or the total ginsenoside composition comprises panaxatriol saponins and panaxadiol saponins; Preferably, the ginsenosides include Rg1 and Re; Preferably, the ginsenosides include Rb1, Rb3, Rc and Rd; Preferably, the ratio of the mass of the ginsenosides to the mass of the ginsenosides is 1.88 to 4.41; Preferably, the mass ratio of Re to Rg1 is 2.31 to 4.41; Preferably, the mass ratio of Rb1 to Re is 0.64 to 1.86; Preferably, the mass ratio of Rb1 to Rd is 0.79 to 2.08; Preferably, the mass ratio of Rb1 to Rc is 0.67 to 2.17; Preferably, the mass ratio of Rb1 to Rb3 is 0.82 to 2.76; Preferably, the mass ratio of Rc to Rb3 is 0.79 to 2.11; Preferably, the mass ratio of Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.54-0.66): (1.917-2.343): (1.953-2.387): (0.9-1.1): (1.143-1.397): (1.908-2.332), for example, about 0.60: about 2.13: about 2.17: about 1.00: about 1.27: about 2.12; Preferably, the mass ratio of Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.684-0.836): (1.944-2.376): (1.242-1.518): (0.9-1.1): (0.567-0.693): (1.566-1.914), for example, about 0.76: about 2.16: about 1.38: about 1.00: about 0.63: about 1.74; Preferably, the mass ratio of Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.333-0.407): (0.774-0.946): (0.9-1.1): (0.9-1.1): (0.423-0.517): (0.576-0.704), for example, about 0.37: about 0.86: about 1.00: about 1.00: about 0.47: about 0.64; Preferably, the mass ratio of Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.252-0.308): (0.594-0.726): (0.684-0.836): (0.9-1.1): (0.612-0.748): (0.468-0.572), for example, about 0.28: about 0.66: about 0.76: about 1.00: about 0.68: about 0.52; Preferably, the mass ratio of Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.351-0.429): (0.819-1.001): (0.675-0.825): (0.9-1.1): (0.504-0.616): (0.594-0.726), for example, about 0.39: about 0.91: about 0.75: about 1.00: about 0.56: about 0.66; Preferably, the mass ratio of Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.207-0.253): (0.819-1.001): (1.251-1.529): (0.9-1.1): (0.981-1.199): (0.819-1.001), for example, about 0.23: about 0.91: about 1.39: about 1.00: about 1.09: about 0.91; Preferably, the mass ratio of Rg1, Re, Rb1, Rc, Rb3 and Rd is (0.189-0.231): (0.684-0.836): (0.909-1.111): (0.9-1.1): (0.981-1.199): (0.657-0.803), for example, about 0.21: about 0.76: about 1.01: about 1.00: about 1.09: about 0.73; preferably, the holographic ginsenoside composition or the total ginsenoside composition further includes Rb2; Preferably, based on the mass of the holographic ginsenoside composition being 100%, the mass percentage of Rg1, Re, Rb1, Rc, Rb2, Rb3 and Rd is greater than 70%; Preferably, the holographic ginsenoside composition comprises the following components in percentage: 3.22% to 7.71% Rg1, 11.99% to 21.87% Re, 12.62% to 19.82% Rb1, 8.42% to 18.82% Rc, 5.22% to 10.45% Rb2, 6.35% to 17.14% Rb3, 9.83% to 17.85% Rd; Preferably, based on the mass of the total ginsenoside composition being 100%, the mass percentage of Rg1, Re, Rb1, Rc, Rb2, Rb3 and Rd is greater than 50%; Preferably, the total ginsenoside composition comprises the following components in percentage: 2.12% to 5.91% Rg1, 9.05% to 16.77% Re, 9.31% to 19.12% Rb1, 6.42% to 14.33% Rc, 3.58% to 7.96% Rb2, 4.87% to 12.94% Rb3, and 7.28% to 13.60% Rd.

4. A method for preparing the ginsenoside composition according to any one of claims 1 to 3, characterized in that: The method comprises the following steps: The total saponins of the original medicinal materials of Panax genus were dissolved and loaded on the reverse phase C 18 In a silica gel chromatography column, elution is first performed with an ethanol aqueous solution having a volume percentage of approximately 43%. When ginsenoside Rb1 is detected, elution is performed with an ethanol aqueous solution having a volume percentage of 50% to 55%. The eluate is collected until ginsenoside Rd is no longer detected in the eluate, and the elution is stopped. The collected eluates are combined to obtain a ginsenoside composition, or fractions of ginsenosides Rb1, Rc, Rb2, Rb3, and Rd are separately collected in combination with online detection and then mixed according to the mass ratio involved in claim 2 to obtain a ginsenoside composition; Alternatively, the total saponins of the original medicinal materials of Panax genus were dissolved and loaded on a reverse phase C 18 In a silica gel chromatography column, elution is first performed with an ethanol aqueous solution having a volume percentage of approximately 30%. When ginsenoside Rg1 is detected, elution is performed with an ethanol aqueous solution having a volume percentage of 50% to 55%. The eluate is collected until ginsenoside Rd is no longer detected in the eluate, and the elution is stopped. The collected eluates are combined to obtain a holographic ginsenoside composition, or fractions of ginsenosides Rg1, Re, Rb1, Rc, Rb2, Rb3, and Rd are separately collected in combination with online detection and then mixed according to the mass ratio involved in claim 3 to obtain a holographic ginsenoside composition; Alternatively, the total saponins of Panax genus raw medicinal materials are mixed according to the mass ratio involved in claim 3 to obtain a total ginsenoside composition.

5. The method according to claim 4, characterized in that The solvent used for the dissolution is an ethanol aqueous solution with a volume percentage of about 30%; Preferably, the mass / volume (mg / mL or g / L) ratio of the total saponins of the Panax genus raw medicinal material to the about 30% ethanol aqueous solution is about 1:(8-12); Preferably, before the sample is loaded, the reverse phase C 18 The silica gel chromatography column was equilibrated; Preferably, the reverse phase C 18 The mass ratio of the silica gel to the total saponins of the Panax raw medicinal material is (7-10):about 1.

6. The preparation method according to claim 4 or 5, characterized in that: The Panax genus raw medicinal materials are selected from one or more of the following: American ginseng roots, American ginseng stems and leaves, ginseng roots, ginseng stems and leaves, and Panax notoginseng stems and leaves; Preferably, the total saponins of Panax genus raw medicinal materials are selected from one or more of the following: total saponins of American ginseng roots, total saponins of American ginseng stems and leaves, total saponins of ginseng roots, total saponins of ginseng stems and leaves, and total saponins of Panax notoginseng stems and leaves; Preferably, in the combination of the total saponins from the roots of American ginseng and the total saponins from the stems and leaves of American ginseng, the mass ratio of the total saponins from the roots of American ginseng to the total saponins from the stems and leaves of American ginseng is about 1:(2-3); Preferably, in the combination of the total saponins from ginseng roots, the total saponins from American ginseng roots, the total saponins from ginseng stems and leaves, and the total saponins from American ginseng stems and leaves, the mass ratio of the total saponins from ginseng roots, the total saponins from American ginseng roots, the total saponins from ginseng stems and leaves, and the total saponins from American ginseng stems and leaves is about 1:about 1:about 1:about 3; Preferably, in the combination of the total saponins from ginseng roots, the total saponins from ginseng stems and leaves, and the total saponins from Panax notoginseng stems and leaves, the mass ratio of the total saponins from ginseng roots, the total saponins from ginseng stems and leaves, and the total saponins from Panax notoginseng stems and leaves is (1-2): about 1: about (1-2); Preferably, in the combination of the total saponins from American ginseng roots, the total saponins from American ginseng stems and leaves, and the total saponins from Panax notoginseng stems and leaves, the mass ratio of the total saponins from American ginseng roots, the total saponins from American ginseng stems and leaves, and the total saponins from Panax notoginseng stems and leaves is about 1:about 1:(1-2); Preferably, the total saponins of Panax genus raw medicinal materials are extracted from the Panax genus raw medicinal materials or are commercial products; Preferably, the total saponins of Panax genus raw medicinal materials are obtained by mixing the respective Panax genus raw medicinal materials and then preparing them using the following method, or by first preparing the total saponins of the respective Panax genus raw medicinal materials separately using the following method and then mixing them: (1) extracting (e.g., percolation extraction) three times using a solvent (e.g., water or an aqueous ethanol solution with a volume percentage of 5% to 95%, such as 50% to 70%), and removing the solvent to obtain a first extract; (2) extracting the first extract three times with n-butanol, combining the extracts to obtain a second extract; (3) separating the second extract by macroporous resin column chromatography, eluting with about 30% ethanol aqueous solution and about 70% ethanol aqueous solution, collecting the eluate with about 70% ethanol, and removing the solvent to obtain a third extract; as well as (4) decolorizing the third extract through a macroporous ion exchange resin, eluting with deionized water, collecting the eluate, and concentrating and drying; Preferably, the macroporous resin is Diaion HP 20 macroporous resin; Preferably, the mass ratio of the macroporous resin to the second extract is (8-10): about 1； Preferably, in the macroporous resin column chromatography, the amount of about 30% ethanol aqueous solution and about 70% ethanol aqueous solution is 3 to 5 column volumes respectively; Preferably, the macroporous ion exchange resin is D201 macroporous anion exchange resin; Preferably, the mass ratio of the macroporous ion exchange resin to the third extract is (8-10): about 1; Preferably, the amount of deionized water used for elution is 4 to 6 column volumes.

7. Use of the ginsenoside composition according to any one of claims 1 to 3 or the ginsenoside composition prepared by the preparation method according to any one of claims 4 to 6 in the preparation of a medicament for preventing and / or treating a disease; Preferably, the ginsenoside composition comprises a total ginsenoside composition (i.e., a first ginsenoside composition), a holographic ginsenoside composition (i.e., a second ginsenoside composition), and / or a ginsenodiol saponin composition (i.e., a third ginsenoside composition); Preferably, the disease includes at least one of the following: nervous system disorders, autoimmune diseases, stress diseases, aging and related diseases, fundus diseases, skin diseases and mitochondrial diseases; Preferably, the neurological disorder comprises at least one of the following: psychiatric disorders, sleep disorders, neurodevelopmental delay and / or developmental disorders, nerve damage and dysfunction diseases, neurodegenerative diseases, addictive diseases and peripheral neuropathy diseases; Preferably, the mental illness includes at least one of the following: schizophrenia, depression, bipolar disorder, anxiety disorder and mania; Preferably, the sleep disorder includes at least one of the following: difficulty falling asleep, difficulty maintaining sleep, early awakening, decreased sleep quality, excessive dreaming, and reduced total sleep time; at the same time, accompanied by daytime functional disorders, such as daytime sleepiness, fatigue, inattention, memory loss, nervousness, compulsion, and depression; Preferably, the neurodevelopmental delay and / or developmental disorder comprises at least one of the following: hyperactivity, inattention, learning disabilities, attention deficit hyperactivity disorder / ADHD, autism, language disorders, sleep disorders, Tourette syndrome / tics and Tourette syndrome; Preferably, the neurological injury and dysfunction diseases include at least one of the following: delirium, perioperative neurocognitive disorder, migraine, epilepsy, neuropsychiatric dysfunction and akinesia sequelae in the acute and chronic stages of stroke, basal ganglia neural circuit dysfunction disease, syndrome, restless legs syndrome, and hypertonia; Preferably, the basal ganglia neural circuit dysfunction disorder includes at least one of the following: chorea, athetosis and dystonia syndrome; Preferably, the neurodegenerative disease comprises at least one of the following: Parkinson's syndrome, Alzheimer's disease, vascular dementia, mixed dementia, secondary dementia, cerebral atrophy, chorea, multiple sclerosis and amyotrophic lateral sclerosis; Preferably, the Parkinson's syndrome includes at least one of the following: multiple system degeneration-Parkinson's plus syndrome, primary Parkinson's syndrome, atypical Parkinson's syndrome, juvenile Parkinson's syndrome, secondary Parkinson's syndrome caused by infection or ischemia, hereditary degenerative Parkinson's syndrome and extrapyramidal reaction caused by drug treatment; Preferably, the multiple system degeneration-parkinsonism plus syndrome includes at least one of the following: multiple system atrophy, progressive supranuclear palsy, dementia with Lewy bodies, brain iron accumulation neurodegeneration type I, diffuse Lewy body disease, Lewy body variant of Alzheimer's disease, corticobasal degeneration and frontotemporal lobar degeneration; Preferably, the addictive disease includes at least one of the following: alcohol and drug addiction, adolescent internet and game addiction, and pathological gambling; Preferably, the peripheral neuropathy disease includes at least one of the following: neuralgia, facial neuritis, hemifacial spasm, multiple peripheral neuropathy, neurodermatitis, Guillain-Barré syndrome, and neuralgia and movement disorders caused by viral infection; Preferably, the autoimmune disease comprises at least one of the following: lupus erythematosus, autoimmune glomerulonephritis, rheumatoid arthritis, dermatomyositis, scleroderma, allergic rhinitis, allergic asthma, urticaria, allergic dermatitis, allergic conjunctivitis, demyelinating disease, connective tissue disease, neuromuscular disease, digestive system disease, endocrine disease and urinary system disease; Preferably, the connective tissue disease comprises at least one of the following: systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis and scleroderma; Preferably, the neuromuscular disease comprises at least one of the following: multiple sclerosis, myasthenia gravis, and demyelinating disease; Preferably, the digestive system disease includes at least one of the following: chronic nonspecific ulcerative colitis, chronic active hepatitis, pernicious anemia and atrophic gastritis; Preferably, the endocrine disease includes at least one of the following: primary adrenocortical Atrophy and chronic goiter; Preferably, the urinary system disease includes autoimmune glomerulonephritis and / or pulmonary-renal hemorrhagic syndrome; Preferably, the stress-induced diseases include sub-health conditions and / or post-stress traumatic sequelae caused by chronic stress; Preferably, the sub-health state includes at least one of the following: insomnia, dreaminess and daytime dysfunction and their related daytime sleepiness, fatigue, inattention, memory loss, reduced work efficiency and creativity, or accompanied by nervousness, anxiety, compulsion and depression; Preferably, the stress trauma sequelae include at least one of the following: acute stress disorder, maladjustment and post-traumatic stress disorder; Preferably, the aging and related diseases include at least one of the following: premature aging, heart aging, memory loss in the elderly, senile hypertension, senile sleep disorders, senile constipation, senile / degenerative urinary frequency and urgency, and chronic inflammation in the elderly; Preferably, the fundus disease includes at least one of the following: retinal vasculitis, retinal vascular occlusion, diabetic retinopathy, optic neuropathy, retinal macular edema and age-related macular degeneration; Preferably, the skin disease comprises at least one of the following: pellagra, drug-induced skin disease and disease-induced skin disease; Preferably, the mitochondrial disease includes mitochondrial myopathy and mitochondrial encephalomyopathy.

8. The use according to claim 7, characterized in that The dosage form of the drug includes liquid preparations and / or solid preparations; Preferably, the liquid preparation includes an oral solution and / or an injection solution; Preferably, the solid preparation is selected from the group consisting of tablets, capsules, granules, pills, enteric-coated preparations, controlled-release preparations and nanoformulations; Preferably, the use includes the use of the ginsenoside composition or the holographic ginsenoside composition as the sole active ingredient and / or the use of the ginsenoside composition or the holographic ginsenoside composition in combination with other drugs to prepare a compound formulation to enhance the synergy and reduce the toxicity of existing drugs; Preferably, the other drugs include at least one of the following drugs: levodopa drugs and dopamine type 2 receptor agonists for treating Parkinson's disease, dopamine for treating schizophrenia and anxiety disorders, Amine receptor inhibitors, sodium / calcium channel inhibitors for treating epilepsy and nerve damage, and for treating neuropsychiatric and behavioral disorders characterized by glutamate hyperexcitability or concurrent GABA inhibition deficiency, mycophenolate mofetil for treating autoimmune diseases and organ transplant rejection, and anti-tumor chemotherapy drugs or targeted drugs; Preferably, the levodopa-type drugs include at least one of the following: Madopar, Sinemet and Darlingfor; Preferably, the dopamine type 2 receptor agonist comprises at least one of the following: sefrol, ropinirole and cabergoline; Preferably, the dopamine receptor inhibitor includes at least one of the following: haloperidol, olanzapine, clozapine and risperidone; Preferably, the sodium and calcium channel inhibitors include at least one of the following: lamotrigine or gabapentin or pregabalin; Preferably, the panaxadiol saponin composition and lamotrigine are used in combination or the composite drug prepared by the two to exert synergistic and toxicity-reducing effects for the treatment of epilepsy, bipolar disorder, and acute cerebral ischemic injury; Preferably, the acute cerebral ischemic injury includes at least one of the following: acute cerebral stroke, neonatal birth canal cerebral ischemia; Preferably, the panaxadiol saponin composition and the gabapentin or pregabalin are used in combination, or the composite drug prepared by the two, when exerting synergistic and toxicity-reducing effects, to treat developmental delay or developmental disorders, alcohol and drug addiction, adolescent internet and game addiction, pathological gambling, neuropathic pain, anxiety, and sleep disorders; Preferably, the chemotherapy drug or target drug includes at least one of the following: paclitaxel and a tyrosine kinase inhibitor.

9. Use of the ginsenoside composition according to any one of claims 1 to 3 or the ginsenoside composition prepared by the preparation method according to any one of claims 4 to 6 in the preparation of health-care products; Preferably, the health care function includes at least one of the following: delaying aging, improving the health level and quality of life of the elderly, improving sub-health status and alleviating the side effects of drug treatment on the nervous system; Preferably, the drug treatment causing nervous system side effects includes neuropsychiatric drugs or Neurological side effects caused by anti-tumor drugs; Preferably, the neuropsychiatric drugs include at least one of the following: dopamine receptor inhibitors and agonists, levodopa drugs, 5-hydroxytryptamine drugs, sodium and calcium channel inhibitors, glutamate receptor inhibitors and other neurotransmitter receptor inhibitors; Preferably, the anti-tumor drug includes at least one of the following: a chemotherapy drug, a molecular targeted drug, and an immunotherapy drug; Preferably, the delaying of aging includes at least one of the following: inhibiting or preventing premature aging, improving memory loss in the elderly, improving sleep in the elderly, increasing appetite, alleviating chronic inflammatory states in the elderly, improving the mobility of the elderly, and prolonging healthy life span; Preferably, the sub-health state includes at least one of the following states: insomnia, dreaminess, sleep disorder, tension, anxiety, depression, memory loss, physical and mental fatigue and reduced work efficiency; Preferably, the health care product comprises a liquid health care product and / or a solid health care product; Preferably, the liquid health care product comprises an oral liquid; Preferably, the solid health care product comprises at least one of the following: tablets, capsules, granules and pills.

10. A preparation comprising the ginsenoside composition according to any one of claims 1 to 3 or the ginsenoside composition prepared by the preparation method according to any one of claims 4 to 6, characterized in that: The preparation comprises at least one of the following ingredients: a nutritional ingredient and an active ingredient; Preferably, the nutritional ingredients include at least one of the following: protein, polypeptide and glutathione precursor amino acids, NAD + precursors and nucleic acids; Preferably, the active ingredients include at least one of the following: extracts of traditional Chinese medicines that are both medicinal and edible, coenzyme Q10, vitamins, and energy metabolism intermediates; Preferably, the dosage form of the preparation is an oral preparation; Preferably, the oral preparation includes a solid preparation and / or a liquid preparation; Preferably, the solid preparation is selected from the group consisting of capsules, ordinary tablets, dispersible tablets, enteric-coated tablets and granules.

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