Use of balesconoside b in combating liver and brain aging

Abstract

The application discloses application of barbatusoside B in resisting liver and brain aging, and belongs to the field of medicinal chemistry. Experimental data of the application show that the barbatusoside B can significantly reduce tissue damage and inflammatory response of the aging liver, improve liver function, and prolong healthy life, and provides a new treatment strategy for resisting liver aging and related diseases; meanwhile, the barbatusoside B can also significantly improve oxidative damage and neural inflammation of the aging brain, protect neuron function, and enhance cognitive ability, and provides a new treatment strategy for resisting brain aging and related neurodegenerative diseases.

Description

Technical Field

[0001] This invention relates to the application of Parishin B (PB) in the treatment of liver and brain aging, and belongs to the field of medicinal chemistry. Background Technology

[0002] As the body ages, its self-repair capabilities and immune defense functions progressively decline, leading to a significant increase in disease susceptibility and mortality. Recent studies have shown that the aging process plays a crucial role in the pathogenesis of various age-related diseases, such as cardiovascular disease, Alzheimer's disease, and malignant tumors. The progressive functional decline of various tissues and organs with age not only causes a comprehensive decline in the immune system and physiological functions but also attracts considerable attention due to its irreversible damage characteristics. Against this backdrop, exploring effective strategies to delay aging and organ function decline has become a focus of attention in contemporary society and a key area of ​​medical research.

[0003] As a vital metabolic center, the liver maintains homeostasis by regulating energy metabolism, biosynthesis, and detoxification of exogenous substances. Characteristic changes in aging livers include abnormal infiltration of immune cells such as macrophages, neutrophils, lymphocytes, and natural killer cells. This chronic low-grade inflammation not only accelerates liver aging but also significantly increases susceptibility to age-related liver diseases such as non-alcoholic fatty liver disease, alcoholic liver disease, liver fibrosis / cirrhosis, and liver cancer. Therefore, developing novel anti-aging drugs to alleviate age-related liver damage is of significant clinical importance for improving the health of the elderly population.

[0004] The brain, one of the most complex organs in the human body, plays a crucial role in maintaining a balance between health and disease. In recent years, the incidence of brain diseases caused by aging has been increasing annually. Brain aging refers to the degenerative changes in the brain's structure and function with age, generally manifesting as a decline in cognitive and motor coordination. Symptoms such as cognitive impairment and decreased learning and memory caused by brain aging not only significantly impact the daily lives of patients but also place a heavy burden on their families and society as a whole. Furthermore, brain aging is a major risk factor for many diseases, including cerebrovascular diseases such as ischemic stroke and neurodegenerative diseases such as Alzheimer's disease and Parkinson's syndrome, posing a significant threat to the health of the elderly. Therefore, there is an urgent need to find new anti-aging drugs to reduce age-related brain damage and improve the health of the elderly.

[0005] Gastrodia elata Bl. is a perennial herbaceous plant, a food and medicine with extremely high nutritional value. It possesses anti-inflammatory, neuroprotective, antioxidant, and antidepressant effects, and has broad research prospects. The chemical components of Gastrodia elata mainly include polyphenols, organic acids, polysaccharides, and nucleotides, among which barisoniol compounds and gastrodin are its main active ingredients. Barisoniol compounds, as the main active ingredients in Gastrodia elata, have received widespread attention from scholars in recent years. They are present in high amounts in Gastrodia elata and possess various pharmacological activities, such as improving memory and anti-tumor effects, showing broad pharmacological effects and application prospects.

[0006] Parishin is the main active ingredient in Gastrodia elata. It is also known that parishin compounds have neuroprotective effects, including improving vascular dementia, neurodegenerative diseases, and anti-epileptic properties. Parishin B (PB) is one of the main active ingredients in Gastrodia elata.

[0007] As a balithoside compound, the application of balithoside B in liver and brain activity is still insufficient. Therefore, it is necessary to conduct in-depth research on new applications of balithoside B in anti-aging pharmacodynamics. Summary of the Invention

[0008] In one aspect of the invention, barisonoside B or a pharmaceutically acceptable salt thereof is provided for the prevention, delay, or treatment of aging in individuals in need of it.

[0009] In another aspect of the invention, a method is provided for preventing, delaying, or treating aging in an individual with such need, the method comprising administering to the individual a therapeutically effective amount of basilidine B or a pharmaceutically acceptable salt thereof.

[0010] The use of basiloxane B or a pharmaceutically acceptable salt thereof in the preparation of medicines or health products for the prevention, delay or treatment of aging.

[0011] The basiloxane B has the molecular formula C. 32 H 40 O 19 It is a basilin derivative isolated from Gastrodia elata: .

[0012] Furthermore, in the above technical solution, the aging is selected from liver aging and / or brain aging.

[0013] Furthermore, in the above technical solution, the pharmaceutically acceptable salt is selected from hydrochloride, sulfate, hydrobromide, hydroiodide, nitrate, hydrogen sulfate, phosphate, acid phosphate, citrate, acetate, oxalate, isonicotinate, lactate, salicylate, acid citrate, tartrate, oleate, tannate, pantothenate, hydrogen tartrate, ascorbate, succinate, maleate, gentianate, fumarate, gluconate, glucuronate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, or pyrazocyanate.

[0014] Furthermore, in the above technical solution, the basiloxane B can prevent, alleviate or reverse one or more pathological features and / or functional impairments of liver and / or brain aging.

[0015] Furthermore, in the above technical solution, the characteristics of liver aging include, but are not limited to: Histological changes in the liver include hepatocellular atrophy, fatty degeneration, inflammatory cell infiltration, fibrosis, and collagen deposition; Abnormal liver function indicators, including elevated serum ALT and AST levels; Abnormal expression of aging-related biomarkers, including upregulation of p16, p21, and p53; Levels of inflammatory factors are elevated, including increased release of pro-inflammatory factors such as TNF-α, IL-6, and IL-1β; The characteristics of brain aging include, but are not limited to: 1) Neurological histological changes, including neuronal atrophy, synapse reduction, amyloid deposition, neurofibrillary tangles, and glial cell proliferation; 2) Abnormal cognitive function indicators, including decreased learning and memory abilities, spatial orientation impairment, and slow reaction time; 3) Increased oxidative stress levels, including increased MDA content in serum or brain tissue and decreased SOD and CAT activity; 4) Abnormal expression of aging-related biomarkers, including upregulated expression of p16, p21, p53, and SA-β-gal; 5) Elevated levels of neuroinflammatory factors, including increased release of pro-inflammatory factors such as IL-6, IL-1β, and TNF-α; 6) Mitochondrial dysfunction, including reduced ATP production in brain cells, decreased mitochondrial membrane potential, and accumulation of mtDNA damage.

[0016] Furthermore, in the above technical solution, the balisine B can delay the progression of liver aging; reduce the severity of liver aging; and / or improve liver function and overall health; the balisine B can delay or halt the progression of brain aging; reduce the severity of brain aging; and / or improve cognitive function and neuroprotective effects.

[0017] Furthermore, in the above technical solution, the balisine B can inhibit the abnormal activation of liver aging-related signaling pathways, including but not limited to: inhibiting the activation of inflammatory signaling pathways and reducing the release of inflammatory factors; regulating the p53 / p21 and p16 / Rb pathways and delaying the cellular aging process; the balisine B can inhibit the abnormal activation of brain aging-related signaling pathways, including but not limited to: activating the AMPK pathway and enhancing antioxidant and energy metabolism regulation capabilities; regulating the p53 / p21 and p16 / Rb pathways and delaying the neuronal aging process.

[0018] Furthermore, in the above-mentioned technical solutions, Barisonoside B can significantly reduce tissue damage and inflammatory response in the aging liver, improve liver function, and prolong healthy lifespan; Barisonoside B can significantly improve oxidative damage and neuroinflammation in the aging brain, protect neuronal function, and enhance cognitive ability; at the same time, Barisonoside B can delay the brain aging process, improve cognitive function, reduce neuronal damage, reduce neuroinflammatory response, and inhibit abnormal activation of aging-related signaling pathways.

[0019] The present invention also provides pharmaceutical compositions or health products for the prevention, delay or treatment of age-related diseases of the brain and / or liver, wherein the active ingredient comprises barisonoside B or a pharmaceutically acceptable salt thereof.

[0020] Furthermore, in the above technical solution, the pharmaceutical composition is used for oral administration, parenteral administration, topical administration, transdermal administration, or rectal administration; the pharmaceutical composition is in the form of tablets, capsules, granules, syrups, patches, suppositories, emulsions, or gels. Attached Figure Description

[0021] Figure 1 Figure showing the effect of basilin B on delaying the senescence of RAW264.7 cells; Figure 2 Figure showing the effect of basiloxane B on improving liver tissue damage in aging mice; Figure 3 This diagram illustrates the regulatory effect of basiloxane B on aging-related factors in the liver tissue of aging mice. Figure 4 Image showing how basaloside B delays aging in Caenorhabditis elegans; Figure 5 A diagram illustrating how basaloside B delays the senescence of HT22 neurons. Figure 6The diagram shows the effect of basilin B on improving learning and memory impairment in aging mice. Figure 7 The diagram shows the effect of basilin B on the ameliorative changes in the pathological features of hippocampal tissue in aging mice. Figure 8 This diagram illustrates the regulatory effect of basiloxane B on the levels of inflammatory and aging-related factors in the hippocampus of aging mice. Detailed Implementation

[0022] The invention will now be described in detail with reference to representative embodiments thereof. These embodiments are merely illustrative and should not be construed as limiting the scope of the invention in any way. Rather, the invention is intended to cover all substitutions, modifications, and equivalents within the scope of the invention as defined in the claims.

[0023] Unless otherwise specified, the technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains.

[0024] The term "barisonoside B" as used in this article has the following structural formula and molecular formula C. 32 H 40 O 19 It is a barine glycoside derivative isolated from Gastrodia elata: .

[0025] As used herein, the term "pharmaceutically acceptable" means that a compound, composition, or carrier is suitable for administration to an individual to achieve the purpose or method described herein without undue harmful side effects.

[0026] As used herein, the term "individual" refers to a mammal or human, including but not limited to primates (monkeys, chimpanzees, gorillas, etc.), rodents (such as rats, mice, gerbils, hamsters, weasels, and rodent-like animals), lagomorphs, suidae (such as pigs, miniature pigs), equines, canids, felines, etc. In a preferred embodiment, the individual is a mammal. In a further preferred embodiment, the individual is a human.

[0027] As used herein, the term “treatment” means the complete or partial cure or elimination of a disease, symptom, or pathological condition, including but not limited to one or a combination of two or more of the following: reducing or eliminating the cause of the disease, symptom, or pathological condition; improving or eliminating its pathological changes; reducing or eliminating one or more of its symptoms and / or signs; slowing or halting its progression; reducing its severity; reducing its morbidity; reducing its recurrence; and improving its prognosis. Anti-liver aging experiment

[0028] This application found through experiments that basiloxane B has significant anti-aging and hepatoprotective effects on animals (e.g., mice) with aging or age-related liver damage. It can delay the aging process of the liver, improve hepatocyte function, reduce liver fibrosis, reduce inflammatory response, and inhibit the abnormal activation of aging-related signaling pathways.

[0029] Therefore, in one aspect, this application provides the use of basiloxane B for the prevention, delay or treatment of liver aging in individuals with such need.

[0030] In some implementations, the basiloxane B can prevent, alleviate, or reverse one or more pathological features and / or functional impairments of liver aging.

[0031] In some implementations, the characteristics of liver aging include, but are not limited to: 1) Histological changes in the liver, including hepatocyte atrophy, fatty degeneration, inflammatory cell infiltration, fibrosis, and collagen deposition; 2) Abnormal liver function indicators, including elevated serum ALT and AST levels; 3) Abnormal expression of aging-related biomarkers, including upregulation of p16, p21, and p53; 4) Increased levels of inflammatory factors, including increased release of pro-inflammatory factors such as TNF-α, IL-6, and IL-1β; In some embodiments, the basiloxane B can slow the progression of liver aging; in other embodiments, it can reduce the severity of liver aging; and / or in some embodiments, it can improve liver function and overall health.

[0032] In some embodiments, the basiloxane B can inhibit the abnormal activation of liver aging-related signaling pathways, including but not limited to: Inhibit the activation of inflammatory signaling pathways and reduce the release of inflammatory factors; It regulates the p53 / p21 and p16 / Rb pathways, thus delaying the cellular senescence process.

[0033] Experimental data from this invention show that basiloxane B can significantly reduce tissue damage and inflammatory response in aging liver, improve liver function, and prolong healthy lifespan, providing a new treatment strategy for combating liver aging and related diseases. Example 1: Barisoniside B can delay the senescence of RAW264.7 cells.

[0034] like Figure 1As shown, D-galactose induced senescence in RAW264.7 cells, which were divided into a control group, a model group, different dose groups, and a positive control group. The effect of balisinoside B on senescent cells was observed using SA-β-gal. The results showed that balisinoside B could reduce SA-β-gal activity in senescent RAW264.7 cells (P < 0.05). The levels of inflammatory factors IL-6, IL-1β, and TNF-α, as well as senescence-related factors p16, p21, and p53, were measured in cells using qPCR; the protein content of p16, p21, and p53 was measured by Western blotting. Compared with the model group, balisinoside B reduced the mRNA levels of IL-6, IL-1β, and TNF-α, as well as the mRNA and protein expression levels of p16, p21, and p53 in D-gal-induced senescent cells (P < 0.05). The results indicate that balisinoside B has a dose-dependent effect on delaying D-gal-induced cell senescence. Example 2: The effect of basiloxane B on improving liver damage in aging mice

[0035] Male C57BL / 6J mice were purchased from Ziyi (Fuzhou) Biotechnology Co., Ltd. (License No.: SCXK(Su)2022-0006). D-galactose (D-gal) was purchased from Shanghai Haoyuan Biomedical Technology Co., Ltd. (purity ≥99%; catalog number HY-N0210; CAS#59-23-4). Parishin B (PB) was purchased from Shanghai Haoyuan Biomedical Technology Co., Ltd. (purity ≥99%; catalog number HY-N2124; CAS#174972-79-3). Metformin (Met) was purchased from Shanghai Yuanye Biotechnology Co., Ltd. (purity ≥99%; catalog number T94272; CAS#657-24-9).

[0036] Eight-week-old male C57BL / 6J mice were acclimatized to experimental conditions for five days and then randomly divided into five groups according to their body weight: a normal control group, a D-gal aging model group, a low-dose PB group (LPB), a high-dose PB group (HPB), and a positive control group (Met). Initial mouse weight was recorded before the experiment. During the experiment, mouse weight was measured weekly. The standard for intraperitoneal injection was 1 mL of drug per 100 g. Model establishment: Except for the normal control group, other groups received daily intraperitoneal injections of D-gal at 150 mg / kg. The normal control group received intraperitoneal injections of physiological saline at the same dose and method for 8 weeks to establish a subacute aging model. Starting from week 5, the low- and high-dose PB groups received daily intraperitoneal injections of PB solution at 1 mg / kg and 5 mg / kg, respectively, while the positive control group received daily intraperitoneal injections of Met solution at 200 mg / kg. At the end of week 8, all experimental mice were sacrificed after fasting but with free access to water.

[0037] Mice were sacrificed after modeling and drug administration. Liver tissue was rapidly placed in 10% formalin solution, followed by routine ethanol dehydration, paraffin embedding, sectioning, and hematoxylin and eosin (HE) staining, Masson staining, and F4 / 80 immunohistochemical staining to observe histopathological changes in the liver tissue. Blood samples were collected by enucleation, incubated at 4°C for 30 minutes, and then centrifuged at 3000 rpm for 15 minutes. Serum was collected and stored after separation. Serum ALT and AST levels were measured using a kit. IL-6, IL-1β, and TNF-α levels in mouse liver tissue were measured by qPCR.

[0038] like Figure 1 As shown, HE staining results revealed that the hepatocytes of the control group mice had clear structure, normal morphology, and clear nucleoli. In the aging group, cell bodies were atrophied, arranged disorderly, and nuclei were pyknoid. After treatment with PB and Met, the hepatocyte morphology of mice in the low-dose PB group, high-dose PB group, and Met group was improved compared to the aging group, with clear cell outlines, orderly arrangement, and clear nucleoli. Masson staining results showed that the hepatocytes of the control group mice were clearly visible, with neatly arranged red fibers and no fibrous connective tissue hyperplasia. In the aging group, there were more blue collagen fibers, disordered hepatocyte arrangement, and collagen fiber hyperplasia. After treatment with PB and Met, liver fibrosis in mice in the low-dose PB group, high-dose PB group, and Met group was improved compared to the aging group, and the proliferation of blue collagen fibers was reduced. F4 / 80 immunohistochemistry showed that compared with the control group, the aging group had a significantly increased number of F4 / 80 positive areas in the liver and increased macrophage infiltration. After treatment with PB and Met, both the PB group and the Met group reduced macrophage infiltration in the liver, indicating that the inflammatory response was suppressed.

[0039] In this experiment, the serum ALT and AST levels of mice were measured. Compared with the control group, the ALT and AST levels in the aging group were significantly increased. Compared with the aging group, the ALT and AST levels in the PB treatment group and the Met treatment group were decreased to varying degrees. The levels of IL-6, IL-1β, and TNF-α in the liver tissue of D-gal-induced aging mice (model group) were significantly increased (P < 0.001), indicating a more severe inflammatory response in the liver of aging mice. Compared with the model group, different doses of balisinoside B significantly reduced the levels of IL-6, IL-1β, and TNF-α in the liver tissue of D-gal-induced aging mice (P < 0.05). The results indicate that balisinoside B has an inhibitory effect on D-gal-induced liver tissue inflammation in aging mice (P < 0.05). Example 3: Regulatory effect of basiloxane B on aging-related factors in liver tissue of aging mice

[0040] A D-gal-induced aging mouse model was established according to the experimental protocol described in Example 2. After modeling, mouse liver tissue was collected to detect the levels of p16, p21, and p53 in the liver tissue using qPCR, and the protein content of p16, p21, and p53 in the liver tissue was determined by Western blotting.

[0041] like Figure 3 As shown, the expression levels of p16, p21, and p53 mRNA and protein in the liver tissue of D-gal-induced aging mice (model group) were significantly increased (P < 0.001). Compared with the model group, high-dose balisinoside B significantly reduced the expression levels of p16, p21, and p53 mRNA and protein in the liver tissue of D-gal-induced aging mice (P < 0.05). These results indicate that balisinoside B has a delaying effect on D-gal-induced liver tissue aging in mice.

[0042] In summary, balisinoside B can significantly improve the histopathological features of liver tissue in aging mice, and significantly reduce the levels of ALT, AST, and inflammatory factors, which are indicators of liver tissue damage in aging mice. Furthermore, balisinoside B can delay the liver aging process by reducing the expression levels of p16, p21, and p53. Anti-brain aging experiment

[0043] This application found through experiments that basiloxane B has significant neuroprotective and anti-aging effects on aging or age-related brain function degeneration in animals (e.g., mice), and can delay the brain aging process, improve cognitive function, reduce neuronal damage, reduce neuroinflammatory response, and inhibit abnormal activation of age-related signaling pathways.

[0044] Therefore, in one aspect, this application provides the use of basiloxane B in a pharmaceutical composition for the prevention, delay or treatment of brain aging in an individual with such need.

[0045] In some implementations, the basiloxane B can prevent, reduce, or reverse one or more pathological features and / or functional impairments of brain aging.

[0046] In some implementations, the characteristics of brain aging include, but are not limited to: 1) Neurological histological changes, including neuronal atrophy, synapse reduction, amyloid deposition, neurofibrillary tangles, and glial cell proliferation; 2) Abnormal cognitive function indicators, including decreased learning and memory abilities, spatial orientation impairment, and slow reaction time; 3) Increased oxidative stress levels, including increased MDA content in serum or brain tissue and decreased SOD and CAT activity; 4) Abnormal expression of aging-related biomarkers, including upregulated expression of p16, p21, p53, and SA-β-gal; 5) Elevated levels of neuroinflammatory factors, including increased release of pro-inflammatory factors such as IL-6, IL-1β, and TNF-α; 6) Mitochondrial dysfunction, including reduced ATP production in brain cells, decreased mitochondrial membrane potential, and accumulation of mtDNA damage.

[0047] In some embodiments, the basiloxane B can delay or halt the progression of brain aging; in other embodiments, it can reduce the severity of brain aging; and / or in some embodiments, it can improve cognitive function and provide neuroprotection.

[0048] In some implementations, the basiloxane B can inhibit the abnormal activation of brain aging-related signaling pathways, including but not limited to: Activate the AMPK pathway to enhance antioxidant and energy metabolism regulation capabilities; Regulating the p53 / p21 and p16 / Rb pathways can delay the aging process of neurons.

[0049] On the other hand, this application also provides the use of Barisoniside B in pharmaceutical compositions for the prevention or treatment of age-related brain diseases such as Alzheimer's disease, Parkinson's disease, vascular dementia, etc.

[0050] Experimental data from this invention show that basiloxane B can significantly improve oxidative damage and neuroinflammation in the aging brain, protect neuronal function, and enhance cognitive ability, providing a new treatment strategy for combating brain aging and related neurodegenerative diseases. Example 4: Barisonin B can delay the aging of Caenorhabditis elegans.

[0051] like Figure 4 As shown, lifespan experiments were first conducted using the model organism *C. elegans*. Barisonoside B extended the lifespan of the nematodes in a dose-dependent manner; and high doses of barisonoside B significantly increased the pharyngeal pump rate and body bending frequency on days 10 and 15 (P < 0.05). By observing lipofuscin and SA-β-gal in the nematodes, barisonoside B reduced lipofuscin accumulation and SA-β-gal activity (P < 0.05); furthermore, barisonoside B improved the survival rate of nematodes under oxidative stress, heat stress, and ultraviolet stress (P < 0.05). These results indicate that barisonoside B can prolong the lifespan of *C. elegans*. Example 5: Barisoniside B can delay the senescence of HT22 neurons.

[0052] like Figure 5As shown, D-galactose-induced senescence of HT22 cells was induced, and the cells were divided into a control group, a model group, different dose groups, and a positive control group. The effect of balisinoside B on senescent HT22 cells was observed using SA-β-gal. The results showed that balisinoside B could reduce SA-β-gal activity in senescent HT22 cells (P < 0.05). The levels of inflammatory factors IL-6, IL-1β, and TNF-α, as well as senescence-related factors p16, p21, and p53 in cells were measured by qPCR; the protein content of p16, p21, and p53 in cells was measured by Western blotting. Compared with the model group, balisinoside B reduced the mRNA levels of IL-6, IL-1β, and TNF-α, as well as the mRNA and protein expression levels of p16, p21, and p53 in D-gal-induced senescent HT22 cells (P < 0.05). The results indicate that balisinoside B has a dose-dependent effect on delaying D-gal-induced cell senescence. Example 6: The effect of basiloxane B on improving learning and memory impairment in aging mice

[0053] Male C57BL / 6J mice were purchased from Ziyi (Fuzhou) Biotechnology Co., Ltd. (License No.: SCXK(Su)2022-0006). D-galactose (D-gal) was purchased from Shanghai Haoyuan Biomedical Technology Co., Ltd. (purity ≥99%; catalog number HY-N0210; CAS#59-23-4). Parishin B (PB) was purchased from Shanghai Haoyuan Biomedical Technology Co., Ltd. (purity ≥99%; catalog number HY-N2124; CAS#174972-79-3). Metformin (Met) was purchased from Shanghai Yuanye Biotechnology Co., Ltd. (purity ≥99%; catalog number T94272; CAS#657-24-9).

[0054] Eight-week-old male C57BL / 6J mice were acclimatized to experimental conditions for five days and then randomly divided into five groups according to their body weight: a normal control group, a D-gal aging model group, a low-dose PB group (LPB), a high-dose PB group (HPB), and a positive control group (Met). Initial mouse weight was recorded before the experiment. During the experiment, mouse weight was measured weekly. The standard for intraperitoneal injection was 1 mL of drug per 100 g. Model establishment: Except for the normal control group, other groups received daily intraperitoneal injections of D-gal at 150 mg / kg. The normal control group received intraperitoneal injections of physiological saline at the same dose and method for 8 weeks to establish a subacute aging model. Starting from week 5, the low- and high-dose PB groups received daily intraperitoneal injections of PB solution at 1 mg / kg and 5 mg / kg, respectively, while the positive control group received daily intraperitoneal injections of Met solution at 200 mg / kg. After model establishment and drug administration, mice underwent a water maze test to investigate the regulatory effect of basilidine B on the learning and memory abilities of aging mice.

[0055] like Figure 6 As shown, in the Morris water maze navigation test, the escape latency of aging mice was significantly increased compared to the control group (P<0.05). Low- and high-dose balisinoside B and positive control treatments significantly reduced the escape latency of the model mice (P<0.05). Subsequently, analysis of the mouse movement trajectories using Smart software revealed no significant difference in movement speed among the groups (P>0.05), but the aging group showed a significant decrease in the number of platform crossings and the time spent in the target quadrant compared to the control group (P<0.05), indicating learning and memory impairment in aging mice. Compared to the aging group, low- and high-dose balisinoside B and positive control treatments increased the number of platform crossings and the time spent in the target quadrant in aging model mice (P<0.05). The results indicate that balisinoside B can improve learning and memory impairment in aging mice, and the therapeutic effect is correlated with the dosage of balisinoside B. Example 7: The effect of basiloxane B on the pathological features of hippocampal tissue in aging mice

[0056] A D-gal-induced aging mouse model was established according to the experimental protocol described in Example 6. After modeling, the mice were sacrificed, and the brain tissue was quickly placed in 10% formalin solution, then routinely dehydrated with ethanol, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (HE) and Nissl to observe changes in the pathological morphology of the brain tissue.

[0057] like Figure 7As shown in the tissue staining results, the hippocampal neurons in the control group mice were neatly arranged, morphologically intact, with uniform cytoplasmic staining and clear nuclear structures. In the aging group mice, the number of hippocampal neurons decreased, their arrangement was disordered, many neurons were shrunken, and the boundary between the cytoplasm and nucleus was unclear. After treatment with PB and Met, the hippocampal neuronal morphology of mice in the low-dose PB group, high-dose PB group, and positive control group was improved compared to the aging group, with clear cell outlines and neat arrangement. Example 8: The regulatory effect of basaloside B on the levels of inflammatory factors and aging-related factors in the hippocampus of aging mice.

[0058] A D-gal-induced aging mouse model was established according to the experimental protocol described in Example 6. After modeling, hippocampal tissue was collected from the mice, and the levels of inflammatory factors IL-6, IL-1β, and TNF-α, as well as aging-related factors p16, p21, and p53 in the hippocampal tissue were measured by qPCR. The protein content of p16, p21, and p53 in the hippocampal tissue was measured by Western blotting.

[0059] like Figure 8 As shown, the levels of IL-6, IL-1β, and TNF-α in the hippocampus of D-gal-induced aging mice (model group) were significantly increased (P < 0.001), indicating a more severe inflammatory response in the hippocampus of aging mice. Compared with the model group, different doses of balisinoside B significantly reduced the levels of IL-6, IL-1β, and TNF-α in the hippocampus of D-gal-induced aging mice (P < 0.05). The results indicate that balisinoside B has an inhibitory effect on D-gal-induced inflammation in the hippocampus of aging mice. The levels of p16, p21, and p53 mRNA and protein expression in the hippocampus of D-gal-induced aging mice (model group) were significantly increased (P < 0.001). Compared with the model group, high doses of balisinoside B more significantly reduced the levels of p16, p21, and p53 mRNA and protein expression in the hippocampus of D-gal-induced aging mice (P < 0.05). The results indicate that balisinoside B has a delaying effect on D-gal-induced aging of the hippocampus in aging mice.

[0060] In summary, balithinosin B exhibits anti-aging effects in both *C. elegans* and cell models. Furthermore, in vivo experiments in mice significantly improved learning and memory performance and histopathological features of the hippocampus in aging mice; it also significantly reduced the levels of inflammatory factors in the hippocampus of aging mice. Secondly, balithinosin B can delay brain aging by reducing the expression levels of p16, p21, and p53.

[0061] All publications and patent applications cited in this application indicate the level of skill in the field to which this disclosure pertains. They are all incorporated herein by reference in their entirety.

[0062] Based on the above description, those skilled in the art can identify the essential features of the present invention and can make various changes and modifications to adapt it to various uses and conditions without departing from the spirit and scope of the invention. All such modifications and alterations are also included within the scope of the invention. Therefore, the scope of the invention should be determined by the appended claims and their legal equivalents.

Claims

1. The use of balisinoside B or a pharmaceutically acceptable salt thereof in the preparation of drugs or health products for the prevention, delay, or treatment of aging, wherein the chemical structural formula of balisinoside B is as follows: 。 2. The application according to claim 1, wherein the aging is selected from liver aging and / or brain aging.

3. The application according to claim 1, wherein the pharmaceutically acceptable salt is selected from hydrochloride, sulfate, hydrobromide, hydroiodide, nitrate, hydrogen sulfate, phosphate, acid phosphate, citrate, acetate, oxalate, isonicotinate, lactate, salicylate, acid citrate, tartrate, oleate, tannate, pantothenate, hydrogen tartrate, ascorbate, succinate, maleate, gentianate, fumarate, gluconate, glucuronide, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, or pyrazocyanate.

4. In the application according to claim 2, the basiloxane B can prevent, alleviate or reverse one or more pathological features and / or functional impairments of liver and / or brain aging.

5. The application according to claim 2, wherein the characteristics of liver aging include, but are not limited to: 1) histological changes in the liver, including hepatocyte atrophy, fatty degeneration, inflammatory cell infiltration, fibrosis, and collagen deposition; 2) abnormal liver function indicators, including elevated serum ALT and AST levels; 3) abnormal expression of aging-related markers, including upregulation of p16, p21, and p53; 4) elevated levels of inflammatory factors, including increased release of pro-inflammatory factors such as TNF-α, IL-6, and IL-1β; and the characteristics of brain aging include, but are not limited to: 1) histological changes in the nervous system, including neuronal atrophy, reduced synapses, and amyloid deposition. 1) Accumulation, neurofibrillary tangles, and glial cell proliferation; 2) Abnormal cognitive function indicators, including decreased learning and memory abilities, spatial orientation impairment, and slow reaction time; 3) Elevated oxidative stress levels, including increased MDA content in serum or brain tissue and decreased SOD and CAT activity; 4) Abnormal expression of aging-related markers, including upregulation of p16, p21, p53, and SA-β-gal; 5) Elevated levels of neuroinflammatory factors, including increased release of pro-inflammatory factors such as IL-6, IL-1β, and TNF-α; 6) Mitochondrial dysfunction, including decreased ATP production in brain cells, decreased mitochondrial membrane potential, and accumulation of mtDNA damage.

6. According to claim 2, the balisine B can delay the progression of liver aging; reduce the severity of liver aging; and / or improve liver function and overall health; the balisine B can delay or halt the progression of brain aging; reduce the severity of brain aging; and / or improve cognitive function and neuroprotective effects.

7. According to claim 2, the balisine B can inhibit the abnormal activation of liver aging-related signaling pathways, including but not limited to: inhibiting the activation of inflammatory signaling pathways and reducing the release of inflammatory factors; regulating the p53 / p21 and p16 / Rb pathways and delaying the cellular aging process; the balisine B can inhibit the abnormal activation of brain aging-related signaling pathways, including but not limited to: activating the AMPK pathway and enhancing antioxidant and energy metabolism regulation capabilities; regulating the p53 / p21 and p16 / Rb pathways and delaying the neuronal aging process.

8. According to the application described in claim 2, basiloxane B can significantly reduce tissue damage and inflammatory response in aging liver, improve liver function, and prolong healthy lifespan; basiloxane B can significantly improve oxidative damage and neuroinflammation in aging brain, protect neuronal function, and enhance cognitive ability; basiloxane B can delay the aging process of brain, improve cognitive function, reduce neuronal damage, reduce neuroinflammatory response, and inhibit abnormal activation of aging-related signaling pathways.

9. A pharmaceutical composition or health product for the prevention, delay, or treatment of age-related diseases of the brain and / or liver, wherein the active ingredient comprises parisonin B or a pharmaceutically acceptable salt thereof, said parisonin B having the following chemical structural formula: 。 10. The pharmaceutical composition or health product according to claim 9, wherein the pharmaceutical composition is for oral administration, parenteral administration, topical administration, transdermal administration or rectal administration; and wherein the pharmaceutical composition is in the form of tablets, capsules, granules, syrups, patches, suppositories, emulsions or gels.

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