A traditional Chinese medicine composition for treating Alzheimer's disease, its preparation method and application

Abstract

The present invention belongs to the technical field of traditional Chinese medicine research, and particularly relates to a traditional Chinese medicine composition for treating Alzheimer's disease, its preparation method and application. The raw materials of the traditional Chinese medicine composition of the present invention and their dosages include: 5-15 parts by weight of Desmodium styracifolium, 10-15 parts by weight of Salvia przewalskii Maxim. var. kansuensis, 9-15 parts by weight of Erythrina arborescens Roxb., 8-20 parts by weight of Euphorbia hirta L., 6-12 parts by weight of Murraya exotica L., and 5-9 parts by weight of Luffa cylindrica (L.) Roem. The traditional Chinese medicine composition has the basic effects of removing dampness and promoting blood circulation to remove stasis, expelling wind and detoxifying, and promoting qi circulation and dredging collaterals. Animal experimental studies have shown that the high-dose and medium-dose of the traditional Chinese medicine composition can improve the learning ability, memory ability, learning and memory retention ability, hippocampal inflammatory mediators, β-amyloid transport enzyme gene and protein expression of Alzheimer's disease Kunming mice. At the same time, the traditional Chinese medicine composition has no effect on the main organ indexes and related body weights of Kunming mice. The proposal of the present invention provides a new technical means for further developing new traditional Chinese medicine drugs for the prevention and treatment of AD.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine research, and particularly relates to a traditional Chinese medicine composition for treating Alzheimer's disease, a preparation method thereof, and an application thereof. Background Art

[0002] Generally speaking, Alzheimer's disease is very common among the elderly population, and its clinical symptoms are also very diverse (Jorfi M, Maaser Hecker A, Tanzi RE. The neuroimmune axis of Alzheimer's disease[J]. Genome Med, 2023, 15(1): 6.). This is related to the fact that it is a common neurodegenerative disease. Alzheimer's disease usually has a relatively heavy economic burden and a relatively high fatality and disability rate, which brings certain economic pressure and related hazards to the elderly (Jia J, Zhang Y, Shi Y, et al. A 19Year Old Adolescent with Probable Alzheimer'sDisease[J]. J Alzheimers Dis, 2023, (3): 915-922.). The pathogenesis of Alzheimer's disease is particularly complex and it is very difficult to cure. In recent years, Alzheimer's disease has received great attention from governments at all levels, social groups, and families and individuals, which is somewhat related to the continuous aging of the population in our country (Murdock MH, Tsai LH. Insights intoAlzheimer's disease from single-cell genomic approaches[J]. Nat Neurosci, 2023, 26(2): 181-195.).

[0003] In the brain tissue of Alzheimer's disease, senile plaques of a certain scale often appear. Such plaques are one of the characteristic morphological structural features of Alzheimer's disease (Soderberg L, Johannesson M, Nygren P, et al. Lecanemab Aducanumab and Gantenerumab Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer's Disease[J]. Neurotherapeutics, 2023, 20(1): 195-206.). It has been confirmed that the main component of senile plaques in Alzheimer's disease is β-amyloid protein. This kind of protein contains a basic structure with special coloring, and there are many substances closely related to neurons around it, including proliferated glial cells, abnormal collagen fibers, neurofibrils, etc. (Stevenson Hoare J, Heslegrave A, Leonenko G, et al. Plasma biomarkers and genetics in the diagnosis and prediction of Alzheimer's disease[J]. Brain, 2023, 146(2): 690-699.). Alzheimer's disease can be detected by detecting β-amyloid protein, glial cells, abnormal collagen fibers, neurofibrils, etc. in the brain tissue. The increase in the content of β-amyloid protein, glial cells, abnormal collagen fibers, neurofibrils, etc. in the brain tissue is often associated with the severity of Alzheimer's disease (Perry G. Alzheimer's Disease Not Just for the Aged[J]. J Alzheimers Dis, 2023, 91(3): 923-924.).

[0004] In fact, after the nerve tissue in the brains of the elderly gradually ages, β-amyloid protein is produced. As the initial initiating factor, it often induces other abnormal substances in the body to approach continuously, especially glial cells, abnormal collagen fibers, neurofibrils, etc. (Mead S, Fox NC. Lecanemab slows Alzheimer's disease hope and challenges[J]. Lancet Neurol, 2023, 22(2): 106-108.). Once the deposition of β-amyloid protein increases, it often triggers a cascading effect in the body, inducing the aggregation of different types of glial cells such as oligodendrocytes, microglia, and astrocytes, accompanied by the aggregation of glial cells, abnormal collagen fibers, neurofibrils, etc. (Chatila ZK, Bradshaw EM. Alzheimer's Disease Genetics A Dampened Microglial Response[J]. Neuroscientist, 2023, 29(2): 245-263.), interfering with the main structure of nerve tissue such as the basic structure of neurons, affecting the generation and conduction of nerve bioelectricity, and ultimately leading to a decrease in the function of the nervous system.

[0005] Currently, the pathogenesis of Alzheimer's disease is still unclear, but it has been confirmed that it is associated with an increase in β-amyloid protein in brain tissue (Cervellati C, Zuliani G. Frontier on Alzheimer's Disease[J]. Int J Mol Sci, 2023, 24(9): 7748.). An increase in β-amyloid protein in the brain tissue of the body, the aggregation of glial cells, abnormal collagen fibers, neurofibrils, etc., these changes often cause mitochondrial activation and the release of a large number of free radicals, and can also promote the activation and aggregation of different types of glial cells such as oligodendrocytes, microglia, and astrocytes (Gonzalez-Ortiz F, Turton M, Kac PR, et al. Brain-derived tau a novel blood based biomarker for Alzheimer's disease-type neurodegeneration[J]. Brain, 2023, 146(3): 1152-1165.), especially the activation and aggregation of microglia, which can release many inflammatory mediators. These inflammatory mediators will stimulate the further activation and aggregation of different types of glial cells such as oligodendrocytes, microglia, and astrocytes, ultimately forming a cascading effect, continuously producing compound effects formed by the accumulation of β-amyloid protein in brain tissue, and ultimately aggravating the condition of Alzheimer's disease.

[0006] As we know, an increase in β-amyloid in the brain tissue, accompanied by the aggregation of glial cells, abnormal collagen fibers, neurofibrils, etc., will gradually accumulate to form senile plaques of various morphologies in different parts of the brain, promoting the occurrence and development of Alzheimer's disease (Beata BK, Wojciech J, Johannes K, et al. Alzheimer's Disease Biochemical and Psychological Background for Diagnosis and Treatment [J]. Int J Mol Sci, 2023, 24(2): 1059.). Generally, there are mainly two types of β-amyloid, such as β-amyloid 1-42 and β-amyloid 1-40 .

[0007] In the brain tissue of Alzheimer's disease, the contents of β-amyloid 1-42 and β-amyloid 1-40 both increase. However, β-amyloid 1-40 is relatively more, and β-amyloid 1-42 is relatively less, but β-amyloid 1-42 has greater toxicity, and β-amyloid 1-40 has lower toxicity (Connolly K, Lehoux M, O'Rourke R, et al. Potential role of chitinase3like protein 1 CHI3L1 / YKL 40 in neurodegeneration and Alzheimer's disease [J]. Alzheimers Dement, 2023, 19(1): 9-24.). Generally, both β-amyloid 1-42 and β-amyloid 1-40 , which are the main components of senile plaques, are present, and there are also neurofibrils, microglial cells, inflammatory mediators, etc. (Aggarwal NT, Mielke MM. Sex Differences in Alzheimer's Disease [J]. Neurol Clin, 2023, 41(2): 343-358.).

[0008] In fact, the β-amyloid 1-42 and β-amyloid 1-40 in the brain tissue of the body can maintain dynamic balance, including β-amyloid 1-42 and β-amyloid 1-40They are all regulatory points for different types of dynamic balance. Ultimately, how they develop and evolve depends on the amyloid-β protein in different parts of the brain tissue. 1-42 and amyloid-β protein 1-40 content change rules (Li S, Huang Y, Yu L, et al. Impact of the Cannabinoid System in Alzheimer's Disease[J]. Curr Neuropharmacol, 2023, 21(3): 715-726.). This change rule also depends on the activation degrees of different types of glial cells such as oligodendrocytes, microglia, and astrocytes.

[0009] Once the dynamic balance of amyloid-β protein 1-42 and amyloid-β protein 1-40 in different regions of the brain tissue is lost, it will promote the further activation of different types of glial cells such as oligodendrocytes, microglia, and astrocytes, and will also cause different degrees of activation of the cell mitochondrial system (Mota IFL, De Lima LS, Santana BM, et al. Alzheimer's Disease Innovative Therapeutic Approaches Based on Peptides and Nanoparticles[J]. Neuroscientist, 2023, 29(1): 78-96.). This will generate a large number of inflammatory mediators and free radicals, and the large number of inflammatory mediators and free radicals will in turn continue to activate different types of glial cells and their mitochondria such as oligodendrocytes, microglia, and astrocytes, forming a waterfall effect in the brain tissue, continuously interfering with the structure and function of the brain tissue. Here, different types of glial cells such as oligodendrocytes, microglia, and astrocytes participate in the feedback effect of the body's brain tissue (Ciurea VA, Covache-Busuioc RA, Mohan AG, et al. Alzheimer's disease 120 years of research and progress[J]. J Med Life, 2023, 16(2): 173-177.).

[0010] In general, inflammatory mediators produced by the further activation of different types of glial cells, such as oligodendrocytes, microglia, and astrocytes, mainly include interleukin-18 (IL-18), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) (Ahmad S, Ahmed SB, Khan A, et al. Natural remedies for Alzheimer's disease A systematic review of randomized controlled trials[J]. Metab Brain Dis, 2023, 38(1): 17-44.). IL-1β, IL-18, IL-6, and TNF-α can stimulate an increase in the number of senile plaques in the brain tissue. The activation of different types of glial cells, such as oligodendrocytes, microglia, and astrocytes, also promotes an increase in the content of inflammatory mediators IL-1β, IL-18, IL-6, and TNF-α. This is related to the imbalance of the 1-42 , β-amyloid 1-40 homeostasis (Twarowski B, Herbet M. Inflammatory Processes in Alzheimer's Disease Pathomechanism Diagnosis and Treatment A Review[J]. Int J Mol Sci, 2023, 24(7): 6518.), is also related to the activation of the cell mitochondrial system to varying degrees, and is more related to the imbalance of the acetylcholine system in the brain tissue.

[0011] It has been confirmed that the brain tissue is one of the relatively closed and important organs, which is related to the existence of the blood-brain barrier composed of continuous vascular endothelium in the brain tissue (Li L, Zhang J, Huang X, et al. Research Progress of Nanocarriers for the Treatment of Alzheimer's Disease[J]. Curr Pharm Des, 2023, 29(2): 95-115.). The intact blood-brain barrier is one of the self-protection devices of the brain tissue. Although β-amyloid exists in the blood 1-42 , β-amyloid 1-40 , and β-amyloid also exists in the brain tissue 1-42 , β-amyloid 1-40, but the blood and brain tissue cannot be exchanged at will. The special protective device between the blood and brain tissue is mainly the blood-brain barrier (Nguyen NM, Cho J, Lee C. Gut Microbiota and Alzheimer's Disease How to Study and Apply Their Relationship[J]. Int J Mol Sci, 2023, 24(4): 4047.). Because of the special protective device between the blood and brain tissue, the basic structure and function of the brain tissue can be effectively protected and maintained at a stable level.

[0012] In order to effectively regulate the level of material exchange between the blood and brain tissue, the body will continuously regulate the β-amyloid protein in the blood and brain tissue 1-42 , β-amyloid protein 1-40 . This regulation requires the participation of special proteins on the blood-brain barrier (Padala SP, Newhouse PA. Blood based biomarkers in Alzheimer's disease a mini-review[J]. Metab Brain Dis, 2023, 38(1): 185-193.). The β-amyloid protein-related transporters that participate in the regulation of β-amyloid protein in the blood and brain tissue 1-42 , β-amyloid protein 1-40 are located on the blood-brain barrier between the blood and brain tissue, including the receptor for advanced glycation end products (RAGE), low density lipoprotein-related protein 1 (LRP1), etc. (Edwards M, Corkill R. Disease-modifying treatments in Alzheimer's disease[J]. J Neurol, 2023, 270(4): 2342-2344.). With RAGE and LRP1, the blood-brain barrier will play a homeostatic regulatory function for β-amyloid protein 1-42 , β-amyloid protein 1-40 .

[0013] Generally speaking, LRP1 on the blood-brain barrier between the blood and brain tissue is a reverse regulatory protein, which also includes apolipoprotein J (Apo J), etc. The specific main function is to transport β-amyloid protein 1-42 , β-amyloid protein 1-40 out of the brain tissue, thereby reducing β-amyloid protein in the brain tissue 1-42 , β-amyloid protein 1-40Content, which has a positive effect on reducing the formation of senile plaques in the brain tissue (Arjmandi-Rad S, Ebrahimnejad M, Zarrindast MR, et al. Do Sleep Disturbances have a Dual Effect on Alzheimer's Disease[J]. Cell Mol Neurobiol, 2023, 43(2): 711-727.), it can be said that LRP1 which promotes the reduction of β-amyloid 1-42 and β-amyloid 1-40 content in the brain tissue is a positive protective factor for Alzheimer's disease.

[0014] Actually, RAGE on the blood-brain barrier between the body's blood and brain tissue is a very important positive regulatory protein, which also includes nuclear transcription factor-κB p65 (NF-κB p65), etc. The specific main function is to transfer β-amyloid 1-42 and β-amyloid 1-40 in the blood into the brain tissue, increasing the β-amyloid 1-42 and β-amyloid 1-40 content in the brain tissue (Lamphere AK, Nieto VK, Kiser JR, et al. Potential mechanisms between periodontitis and Alzheimer's disease a scoping review[J]. Can J Dent Hyg, 2023, 57(1): 52-60.). This plays a negative auxiliary role in promoting the physiological function of the brain tissue and is not conducive to the rehabilitation treatment of Alzheimer's disease. It can be said that RAGE which promotes the increase of β-amyloid 1-42 and β-amyloid 1-40 content in the brain tissue is a negative protective factor for Alzheimer's disease (Fujikawa R, Tsuda M. The Functions and Phenotypes of Microglia in Alzheimer's Disease[J]. Cells, 2023, 12(8): 1207.).

[0015] At present, there are many drugs for treating Alzheimer's disease, such as vitamin B6 (Liu XX, Wu PF, Liu YZ, et al. Association Between Serum Vitamins and the Risk of Alzheimer's Disease in Chinese Population[J]. J Alzheimers Dis, 2022, 85(2): 829-836.), estrogen, anti-β-amyloid, nano-selenium, anti-apoptosis drugs, antioxidants, vitamin D, etc. However, these vitamin B6 (Ettinger S. Diet Gut Microbiome and Cognitive Decline[J]. Curr Nutr Rep, 2022, 11(4): 643-652.), estrogen, anti-β-amyloid, nano-selenium, anti-apoptosis drugs, antioxidants, vitamin D, etc. often have relatively obvious side effects, lack the overall regulatory effect of drugs, the interaction effect between drugs, and many vitamin B6 (Kalecky K, Ashcraft P, Bottiglieri T. One Carbon Metabolism in Alzheimer's Disease and Parkinson's Disease Brain Tissue[J]. Nutrients, 2022, 14(3): 599.), estrogen, anti-β-amyloid, nano-selenium, anti-apoptosis drugs, antioxidants, vitamin D, etc. often have obvious side effects. Therefore, it is very important to study traditional Chinese medicine with an overall effect and fewer side effects, which will actively overcome the deficiencies of vitamin B6 (Wang Z, Zhu W, Xing Y, et al. B vitamins and prevention of cognitive decline and incident dementia a systematic review and meta-analysis[J]. Nutr Rev, 2022, 80(4): 931-949.), estrogen, anti-β-amyloid, nano-selenium, anti-apoptosis drugs, antioxidants, vitamin D, etc. Summary of the Invention

[0016] The object of the present invention is to solve the deficiencies of the prior art and provide a traditional Chinese medicine composition for treating Alzheimer's disease, its preparation method and application. The specific technical solution is as follows:

[0017] A traditional Chinese medicine composition for treating Alzheimer's disease, the raw materials of the above traditional Chinese medicine composition and their dosages include: 5-15 parts by weight of Desmodium styracifolium, 10-15 parts by weight of Salvia przewalskii Maxim. var. mandarinorum (Diels) Stib., 9-15 parts by weight of Erythrophleum fordii Oliv., 8-20 parts by weight of Euphorbia hirta L., 6-12 parts by weight of Murraya exotica L., 5-9 parts by weight of Luffa cylindrica (L.) Roem. var. hypoleuca Hand.-Mazz.

[0018] The traditional Chinese medicine composition provided by the present invention includes 6 kinds of medicinal materials. Among them, Desmodium styracifolium, also known as Pogostemon cablin (Blanco) Benth., Medicago hispida Gaertn., Lysimachia paridiformis Franch. var. cephalantha Franch., Lespedeza cuneata (Dum. Cours.) G. Don, is cool in nature, bitter and pungent in taste, and belongs to the basic meridians of the stomach meridian, spleen meridian and liver meridian of the body, and has the main effects of removing dampness and strengthening the stomach, relieving summer heat and regulating the middle energizer; Salvia przewalskii Maxim. var. mandarinorum (Diels) Stib., also known as Salvia przewalskii Maxim., Salvia miltiorrhiza Bunge, Gentiana macrophylla Pall., is slightly cold in nature, bitter in taste, and belongs to the basic meridians of the liver meridian and heart meridian of the body, and has the main effects of promoting blood circulation to remove stasis, relieving vexation and pain, promoting granulation and regulating menstruation, discharging pus and nourishing the heart; Erythrophleum fordii Oliv., also known as Hero bark, Kapok bark, Erythrophleum fordii Oliv., is slightly cold in nature, slightly bitter and pungent in taste, and belongs to the basic meridians of the kidney meridian and liver meridian of the body, and has the main effects of expelling wind and activating collaterals, reducing swelling and removing dampness, promoting diuresis and dredging meridians; Euphorbia hirta L., also known as Euphorbia thymifolia L., Euphorbia hirta L., Euphorbia hirta L., is cold in nature, sour and pungent in taste, and belongs to the basic meridians of the liver meridian and lung meridian of the body, and has the main effects of detoxifying and promoting dampness, clearing heat and relieving itching; Murraya exotica L., also known as Murraya paniculata (L.) Jack., Murraya paniculata (L.) Jack., Murraya paniculata (L.) Jack., is warm in nature, slightly bitter and pungent in taste, and belongs to the basic meridians of the stomach meridian and liver meridian of the body, and has the main effects of promoting qi circulation and dispersing stasis, relieving pain and promoting blood circulation; Luffa cylindrica (L.) Roem. var. hypoleuca Hand.-Mazz., also known as Luffa acutangula (L.) Roxb., Luffa cylindrica (L.) Roem., Luffa cylindrica (L.) Roem., is neutral in nature, sweet in taste, and belongs to the basic meridians of the liver meridian, stomach meridian and lung meridian of the body, and has the main effects of dredging collaterals and removing dampness, reducing fire and dredging meridians.

[0019] As a further preferred embodiment, the raw materials of the above traditional Chinese medicine composition and their dosages include: 10 parts by weight of Desmodium styracifolium, 12 parts by weight of Salvia przewalskii Maxim. var. mandarinorum (Diels) Stib., 12 parts by weight of Erythrophleum fordii Oliv., 20 parts by weight of Euphorbia hirta L., 9 parts by weight of Murraya exotica L., 7 parts by weight of Luffa cylindrica (L.) Roem. var. hypoleuca Hand.-Mazz.

[0020] The traditional Chinese medicine composition in the present invention has the main basic effects of removing dampness and promoting blood circulation, expelling wind and detoxifying, promoting qi circulation and dredging collaterals. Relevant animal experiments show that the large dose (18.20 g / kg) and medium dose (9.10 g / kg) of the traditional Chinese medicine composition can improve the learning ability, memory ability, learning and memory retention ability, hippocampal inflammatory mediators, β-amyloid transporter gene and protein expression of Alzheimer's disease Kunming mice (male animals). At the same time, the traditional Chinese medicine composition has no effect on the main organ indexes and related body weights of Kunming mice (male animals), indicating that the traditional Chinese medicine composition composed of Desmodium styracifolium, Salvia przewalskii Maxim. var. mandarinorum (Diels) Stib., Erythrophleum fordii Oliv., Euphorbia hirta L., Murraya exotica L., Luffa cylindrica (L.) Roem. var. hypoleuca Hand.-Mazz. is effective in treating Alzheimer's disease and has no side effects.

[0021] Furthermore, the present invention also provides a clinically suitable traditional Chinese medicine preparation for treating Alzheimer's disease, which is prepared from the traditional Chinese medicine composition described in the present invention by adding excipients required for preparation of the pharmaceutical preparation according to the conventional methods for preparing pharmaceutical preparations.

[0022] As a further preferred embodiment, the above excipients include one or more of starch, microcrystalline cellulose, sucrose, lactose, powdered sugar, glucose, and vitamin C.

[0023] As a further preferred embodiment, the above traditional Chinese medicine preparation is a decoction, a capsule, a pill, a granule, a tablet, or an oral liquid.

[0024] The present invention also provides a method for preparing the above traditional Chinese medicine composition, which includes the following steps:

[0025] (1) Weigh each raw material medicine according to the parts by weight of the above traditional Chinese medicine composition, mix the raw material medicines evenly, add distilled water 5 - 15 times the total weight of the medicine, soak for 1 - 2 hours, decoct for 1 - 2.5 hours, and then cool.

[0026] (2) Filter the medicinal liquid cooled in step (1) with gauze to obtain the first filtrate and the filter residue.

[0027] (3) Add distilled water with the same volume as that in step (1) to the remaining medicinal residue in step (2), repeat steps (1) and (2) to obtain the second filtrate, and then merge and mix the first filtrate and the second filtrate to obtain the decoction of the traditional Chinese medicine composition for treating Alzheimer's disease.

[0028] As a further preferred embodiment, dry the above decoction at 60°C - 80°C for 4d - 6d to obtain the dry extract of the traditional Chinese medicine composition.

[0029] As a further preferred embodiment, pulverize, grind, and filter the above dry extract to obtain the dry powder of the traditional Chinese medicine composition.

[0030] As a further preferred embodiment, the filtration is carried out with gauze, and filtration is carried out successively with 2 - layer gauze, 4 - layer gauze, and 6 - layer gauze.

[0031] The beneficial effects of the present invention are as follows: The present invention provides a traditional Chinese medicine composition that can be applied in the preparation of drugs for treating Alzheimer's disease. In the traditional Chinese medicine composition provided by the present invention, the monarch drugs, Herba Desmodii Sapurpurei and Salvia przewalskii Maxim. var. kansuensis (E. Peter) Y. W. Li, mainly have the basic effects of removing dampness and promoting blood circulation to remove stasis; the ministerial drugs, Erythrophleum fordii Oliv. and Euphorbia hirta L., mainly have the basic effects of expelling wind and detoxifying; the adjuvant drug, Murraya exotica L., has the basic effect of promoting qi circulation; and the guiding drug, Luffa cylindrica (L.) Roem. var. ovifera (L.) Roem., has the basic effect of dredging collaterals. Animal studies of the present invention show that the high dose (18.20 g / kg) and medium dose (9.10 g / kg) of the traditional Chinese medicine composition provided by the present invention can improve the learning ability, memory ability, learning and memory retention ability, hippocampal inflammatory mediators, β-amyloid transporter gene and protein expression of Alzheimer's disease Kunming mice (male animals). At the same time, the traditional Chinese medicine composition has no effect on the main organ indices and related body weights of Kunming mice (male animals). Therefore, the main effects of the traditional Chinese medicine composition of the present invention are to remove dampness and promote blood circulation to remove stasis, expel wind and detoxify, and promote qi circulation and dredge collaterals. The traditional Chinese medicine composition composed of Herba Desmodii Sapurpurei, Salvia przewalskii Maxim. var. kansuensis (E. Peter) Y. W. Li, Erythrophleum fordii Oliv., Euphorbia hirta L., Murraya exotica L., and Luffa cylindrica (L.) Roem. var. ovifera (L.) Roem. is effective against Alzheimer's disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 Shows the effect of the traditional Chinese medicine composition on the learning ability of Alzheimer's disease Kunming mice (male animals);

[0033] Figure 2 Shows the effect of the traditional Chinese medicine composition on the memory ability of Alzheimer's disease Kunming mice (male animals);

[0034] Figure 3 Shows the effect of the traditional Chinese medicine composition on the learning and memory retention ability of Alzheimer's disease Kunming mice (male animals);

[0035] Figure 4 Shows the effect of the traditional Chinese medicine composition on hippocampal β-amyloid protein 1-40 of Alzheimer's disease Kunming mice (male animals);

[0036] Figure 5 Shows the effect of the traditional Chinese medicine composition on hippocampal IL-1β of Alzheimer's disease Kunming mice (male animals);

[0037] Figure 6 Shows the effect of the traditional Chinese medicine composition on hippocampal IL-6 of Alzheimer's disease Kunming mice (male animals);

[0038] Figure 7 Shows the effect of the traditional Chinese medicine composition on hippocampal TNF-α of Alzheimer's disease Kunming mice (male animals);

[0039] Figure 8 Shows the effect of the traditional Chinese medicine composition on hippocampal RAGE protein of Alzheimer's disease Kunming mice (male animals);

[0040] Figure 9 Shown is the effect of the traditional Chinese medicine composition on the LRP1 protein in the hippocampus of Alzheimer's disease Kunming mice (male animals);

[0041] Figure 10 Shown is the effect of the traditional Chinese medicine composition on the RAGE gene in the hippocampus of Alzheimer's disease Kunming mice (male animals);

[0042] Figure 11 Shown is the effect of the traditional Chinese medicine composition on the LRP1 gene in the hippocampus of Alzheimer's disease Kunming mice (male animals);

[0043] Figure 12 Shown is the effect of the traditional Chinese medicine composition on the kidney index and lung index of Alzheimer's disease Kunming mice (male animals);

[0044] Figure 13 Shown is the effect of the traditional Chinese medicine composition on the liver index and heart index of Alzheimer's disease Kunming mice (male animals);

[0045] Figure 14 Shown is the effect of the traditional Chinese medicine composition on the body weight of Alzheimer's disease Kunming mice (male animals). Detailed implementation mode

[0046] The concept, specific structure and technical effects of the present invention will be clearly and completely described below in combination with the embodiments and the drawings to fully understand the purpose, scheme and effects of the present invention.

[0047] Example 1

[0048] A traditional Chinese medicine composition for treating Alzheimer's disease, the raw materials of the traditional Chinese medicine composition and their dosages include: 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii Maxim. var. kansuensis, 12 g of Erythrophleum fordii Oliv., 20 g of Euphorbia hirta L., 9 g of Murraya exotica L., and 7 g of Luffa cylindrica (L.) Roem.

[0049] Example 2

[0050] The preparation of a traditional Chinese medicine composition (decoction) for treating Alzheimer's disease includes the following steps:

[0051] (1) Weigh 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii Maxim. var. kansuensis, 12 g of Erythrophleum fordii Oliv., 20 g of Euphorbia hirta L., 9 g of Murraya exotica L., and 7 g of Luffa cylindrica (L.) Roem. respectively, and uniformly mix them to obtain 70 g of the traditional Chinese medicine composition. A total of 6 portions of this traditional Chinese medicine composition are prepared to obtain 420 g of the traditional Chinese medicine composition. Then, the mixture of 420 g of the medicinal materials is cut into pieces and put into a 20000 mL round-bottom flask, and 6200 mL of distilled water is added; soak for 2 hours and decoct for 2.2 hours, and control the decocting temperature at 80 °C;

[0052] (2) Filter the medicated liquid cooled in step (1) successively through two layers of gauze, four layers of gauze, and six layers of gauze to obtain the first filtrate and the drug residue.

[0053] (3) Add distilled water with the same volume as that in step (1) to the residue of the traditional Chinese medicine composition obtained in step (2), soak the residue of the traditional Chinese medicine composition for 2 h, decoct the residue of the traditional Chinese medicine composition for 2.2 h, and filter to obtain the second filtrate of the traditional Chinese medicine composition.

[0054] (4) Combine and mix the first filtrate of the traditional Chinese medicine composition and the second filtrate of the traditional Chinese medicine composition to obtain the decoction of the traditional Chinese medicine composition for treating Alzheimer's disease.

[0055] Example 3

[0056] Preparation of a traditional Chinese medicine composition (dry extract) for treating Alzheimer's disease, comprising the following steps:

[0057] Place the decoction obtained in Example 2 in a forced-air drying oven at a temperature of 65 °C for drying for 6 days to obtain 89 g of the dry extract of the traditional Chinese medicine composition. The extract yield of the dry extract of the traditional Chinese medicine composition is calculated as (89 g / 420 g) × 100% = 21.19%.

[0058] Example 4

[0059] Preparation of a traditional Chinese medicine composition (dry powder) for treating Alzheimer's disease, comprising the following steps:

[0060] Place the dry extract of the traditional Chinese medicine composition obtained in Example 3 in a pulverizer for pulverization three times, grind, and filter successively through 40-mesh, 80-mesh, and 200-mesh sieve meshes to obtain 85 g of the dry powder of the traditional Chinese medicine composition. The powder yield of the dry powder of the traditional Chinese medicine composition is (85 g / 420 g) × 100% = 20.24%.

[0061] Example 5

[0062] Pharmacodynamic experiment of the traditional Chinese medicine composition of the present invention in treating Alzheimer's disease

[0063] 1. Experimental materials

[0064] 1.1 Analysis object

[0065] 140 experimental animals, Kunming mice (male), 3.5 months old, body weight (21.5 ± 1.5) g, provided by Beijing Vital River Laboratory Animal Technology Co., Ltd. (SCXK(Beijing)2019-0001). The Kunming mice (male) were raised in the standard experimental animal center (Heilongjiang University of Chinese Medicine). The appropriate humidity and temperature of the Kunming mice (male) were maintained in the breeding environment. Appropriate food, drinking water, bedding, etc. required for the life of the Kunming mice (male) were provided. Ventilation treatment was given to the Kunming mice (male) every day, and the conditions of the experimental Kunming mice (male) were observed at any time to conduct a comprehensive evaluation of the Kunming mice (male).

[0066] 1.2 Analytical instruments

[0067] Experimental electrothermal thermostatic incubator, produced by Shanghai Wuju Co., Ltd., model HH-11420; experimental electronic balance, produced by Sartorius Co., Ltd., model PLZOZ-S; experimental stereotaxic apparatus, produced by Hebei Huicai Co., Ltd., model ZH-C; experimental color analysis system, produced by Wuhan Qianping Imaging Co., Ltd., model HMIAS; experimental Morris water maze, produced by Anhui Huaibei Zhenghua Co., Ltd., model MWM101; experimental tabletop centrifuge, produced by Shanghai Anting Factory, model TGL16G; experimental quantitative PCR instrument, produced by Applied Biosystems (USA); embedding machine, produced by Changzhou Zhongwei Co., Ltd., model BMJB; -80 °C refrigerator, produced by Sanyo Co., Ltd. (Japan), model MDF-U3386S; microplate reader, produced by RT Co., Ltd. (USA), model 6100.

[0068] 1.3 Analytical drugs

[0069] The traditional Chinese medicine composition composed of 10 g of Pogostemon cablin, 12 g of Salvia miltiorrhiza Bge. var. przewalskii, 12 g of Erythrophleum fordii Oliv., 20 g of Euphorbia hirta L., 9 g of Murraya exotica L., and 7 g of Luffa cylindrica (L.) Roem. was used in the experiment. It was entrusted to (Heilongjiang University of Chinese Medicine) for procurement; the procurement location was the First Affiliated Hospital of Heilongjiang University of Chinese Medicine (Heilongjiang University of Chinese Medicine); it was entrusted to (Heilongjiang University of Chinese Medicine) for processing, identification, and evaluation in accordance with the standards of the National Medical Products Administration; it was entrusted to (Heilongjiang University of Chinese Medicine) for the analysis and treatment of the formula; the traditional Chinese medicine composition composed of 10 g of Pogostemon cablin, 12 g of Salvia miltiorrhiza Bge. var. przewalskii, 12 g of Erythrophleum fordii Oliv., 20 g of Euphorbia hirta L., 9 g of Murraya exotica L., and 7 g of Luffa cylindrica (L.) Roem. was prepared into the required decoction, dry extract, dry powder, etc., and stored at low temperature for later use.

[0070] 1.4 Analytical reagents

[0071] Donepezil tablets, produced by Chongqing Zhien Pharmaceutical Co., Ltd., batch number 20191201; β-amyloid 1-40, produced by Nanjing Jiancheng Co., Ltd., batch number 20170901; IL-6 and IL-1β, from Sigma Company, USA; β-amyloid protein 1-42 (Nanjing Jiancheng Co., Ltd.); RAGE, β-action (from Santa Cruz Biotechnology, Inc., USA); other drugs and reagents were provided by (Qiqihar Medical College), Professor Zhang Maoxiang (Guangxi Zhuang Autonomous Region Engineering Research Center for the Construction and Application of Traditional Chinese Medicine In Vivo Pharmacochemistry Database), and Professor Li Baolong (Heilongjiang University of Chinese Medicine).

[0072] 2. Analytical method

[0073] 2.1 Grouping of analysis objects

[0074] This invention patent lists 140 Kunming mice (male animals) as the analysis objects, adapts to raise Kunming mice (male animals) for 1 week, and groups Kunming mice (male animals) according to the random number table. It is mainly divided into 7 groups, namely the observation negative group, the sham operation group, the model observation group, the positive analysis group, the high-dose intervention group of traditional Chinese medicine composition (referred to as the high-dose intervention group), the medium-dose intervention group of traditional Chinese medicine composition (referred to as the medium-dose intervention group), and the low-dose intervention group of traditional Chinese medicine composition (referred to as the low-dose intervention group). The number of Kunming mice (male animals) in each group is 20. They are caged separately, observed daily, and given sufficient daily necessities.

[0075] 2.2 Replication of the analysis model

[0076] This invention patent uses β-amyloid protein to prepare the model 1-42 , inject β-amyloid protein 1-42 into the hippocampal region of Kunming mice (male animals), determine Kunming mice (male animals) as the analysis objects, anesthetize Kunming mice (male animals), fix the limbs and head of Kunming mice (male animals), wet and cut off the hair on the head of Kunming mice (male animals), fully expose the scalp of the head of Kunming mice (male animals), disinfect the scalp of the head of Kunming mice (male animals), and under sterile operation, use scissors to cut open the skin of the head of Kunming mice (male animals), use a locator to locate the hippocampal region of Kunming mice (male animals), and drill a hole in the hippocampal region of this Kunming mouse (male animal). Prepare β-amyloid protein 1-42Suspension (5 μL of 80 pmol / μL in the condensed state). Use a micropipette to withdraw 5 μL of the 80 pmol / μL suspension in the condensed state, and inject it into the confirmed hippocampal region of Kunming mice (male animals) using the micropipette. Leave the needle in place for 3 minutes. Seal the pores of Kunming mice (male animals) with sterile materials to prevent infection. To prevent infection, add gentamicin (an antibiotic) dropwise to the pores of Kunming mice (male animals). Keep Kunming mice (male animals) in single cages and observe them at any time to avoid infection. The sham operation group mainly simulates the surgical process and does not receive the 5 μL of 80 pmol / μL suspension in the condensed state. The observation negative group does not require intervention and does not receive the 5 μL of 80 pmol / μL suspension in the condensed state. After a series of treatments, 20 Kunming mice (male animals) survived in the observation negative group; 18 Kunming mice (male animals) survived in the sham operation group; 15 Kunming mice (male animals) survived in the model observation group; 17 Kunming mice (male animals) survived in the positive analysis group; 16 Kunming mice (male animals) survived in the high-dose intervention group; 16 Kunming mice (male animals) survived in the medium-dose intervention group; 18 Kunming mice (male animals) survived in the low-dose intervention group. The number of surviving animals in each group met the expectations, and subsequent experimental studies could be carried out.

[0077] 2.3 Conversion of drug dosage

[0078] The dosage of the traditional Chinese medicine composition for Kunming mice (male animals) needs to be converted. The total of 70 g of the traditional Chinese medicine composition consisting of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrophleum fordii, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica (L.) Roem. is the human safe dosage. The medium dosage of the dosage for Kunming mice (male animals) is 70 g × 0.0026 / 0.02 kg = 9.10 g / kg, which is the medium dosage of the traditional Chinese medicine composition consisting of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrophleum fordii, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica (L.) Roem. The high dosage of the traditional Chinese medicine composition consisting of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrophleum fordii, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica (L.) Roem. is calculated as 70 g × 0.0026 / 0.02 kg × 2 = 18.20 g / kg. The low dosage of the traditional Chinese medicine composition consisting of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrophleum fordii, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica (L.) Roem. is calculated as 70 g × 0.0026 / 0.02 kg / 2 = 4.55 g / kg. Similarly, the effective safe dosage of donepezil is calculated as 0.001 g / kg. Select the high dosage of the traditional Chinese medicine composition consisting of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrophleum fordii, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica (L.) Roem. as 70 g × 0.0026 / 0.02 kg × 2 = 18.20 g / kg, the medium dosage as 70 g × 0.0026 / 0.02 kg = 9.10 g / kg, the low dosage as 70 g × 0.0026 / 0.02 kg / 2 = 4.55 g / kg, and its effective safe dosage of donepezil as 0.001 g / kg to conduct experimental research.

[0079] 2.4 Administration of the analysis object

[0080] After 1 week of environmental adaptation, male Kunming mice began the drug administration schedule. The male Kunming mice in the negative group, model observation group, and sham operation group were all given an equal amount of normal saline by gavage, and were observed at any time to avoid accidents to the male Kunming mice; the male Kunming mice in the positive analysis group were given donepezil at a dose of 0.001 g / kg by gavage, and were observed at any time to avoid accidents to the male Kunming mice; the male Kunming mice in the high-dose intervention group were given a gavage equivalent to 18.20 g / kg of the crude herbs of the traditional Chinese medicine composition (a traditional Chinese medicine composition consisting of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrophleum fordii, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica), and were observed at any time to avoid accidents to the male Kunming mice; the male Kunming mice in the medium-dose intervention group were given a gavage equivalent to 9.10 g / kg of the crude herbs of the traditional Chinese medicine composition (a traditional Chinese medicine composition consisting of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrophleum fordii, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica), and were observed at any time to avoid accidents to the male Kunming mice; the male Kunming mice in the low-dose intervention group were given a gavage equivalent to 4.55 g / kg of the crude herbs of the traditional Chinese medicine composition (a traditional Chinese medicine composition consisting of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrophleum fordii, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica), and were observed at any time to avoid accidents to the male Kunming mice. The drug administration time for the male Kunming mice in each group was 28 days, and the male Kunming mice in each group were observed at the same time, and were observed at any time to avoid accidents to the male Kunming mice.

[0081] 2.5 Detection of learning and memory ability

[0082] The Morris water maze was used to detect the learning and memory level. It was necessary to keep the environment stable and quiet. The designated standing platform was placed in the fourth quadrant, the water temperature was controlled at (23.5±2.5) °C, the designated standing platform was 1.6 cm below the water surface, the water depth in the pool was controlled at 20 cm, and the internal and external reference objects needed to be consistent to avoid interference to the male Kunming mice. The head of the male Kunming mice was stained with India ink, and the male Kunming mice were placed in different quadrants of the detection instrument and trained for 4 days, with each training time being 60 s. If the male Kunming mice could not find the designated standing platform within 60 s, the male Kunming mice needed to stay on the designated standing platform for 15 s. The swimming trajectories of the male Kunming mice were recorded and photographed using a camera. After 5 days of training, the designated standing platform was removed, and the learning ability (latency), memory ability (swimming distance), and learning and memory retention ability (time staying in the target quadrant) could be detected for comprehensive evaluation.

[0083] 2.6 Detection of hippocampal inflammatory mediators

[0084] After the learning ability (latency), memory ability (swimming distance), and learning and memory retention ability (time staying in the target quadrant) of each group of Kunming mice (male animals) were measured, the measurement and analysis were carried out. Prepare an ice table for dissecting Kunming mice (male animals). The operator wears protective gloves, grabs the tail of the Kunming mouse (male animal) with the right hand, and dislocates the cervical vertebra of the Kunming mouse (male animal) with the left hand to execute it. Cut off the head of the Kunming mouse (male animal), remove the skin of the Kunming mouse (male animal), cut open the skull from behind the head of the Kunming mouse (male animal) to fully expose the whole brain of the Kunming mouse (male animal), clean the whole brain of the Kunming mouse (male animal), remove the redundant parts of the Kunming mouse (male animal) such as the brainstem, effectively dissect the hippocampal tissue of the Kunming mouse (male animal) on the ice table, homogenize the hippocampal tissue of the Kunming mouse (male animal), centrifuge the hippocampal tissue of the Kunming mouse (male animal) at 3000 rpm / min with a tabletop centrifuge, extract the supernatant of the hippocampal tissue of the Kunming mouse (male animal), aliquot the supernatant of the hippocampal tissue of the Kunming mouse (male animal), detect the protein content in the hippocampus of the Kunming mouse (male animal), and store the remaining supernatant of the hippocampal tissue of the Kunming mouse (male animal) in a low-temperature refrigerator for future use. Process according to the detection instructions, measure the absorbance value (OD) at a wavelength of 450 nm, and calculate the expression level of inflammatory mediators in the hippocampal tissue of the Kunming mouse (male animal).

[0085] 2.7 Determination of hippocampal protein expression

[0086] After the learning ability (latency), memory ability (swimming distance), and learning and memory retention ability (time spent in the target quadrant) of each group of Kunming mice (male animals) were measured, protein expression analysis was performed. Prepare an ice table for dissecting Kunming mice (male animals). The operator wears protective gloves, grabs the tail of the Kunming mouse (male animal) with the right hand, grabs the Kunming mouse (male animal) with the left hand, and can use 10% chloral hydrate for anesthesia with a syringe in the right hand. After the Kunming mouse (male animal) is anesthetized, fix the four limbs of the Kunming mouse (male animal), and also fix the head of the Kunming mouse (male animal). Locate the most obvious pulsation point in the chest area of the Kunming mouse (male animal), use scissors to cut open the chest skin of the Kunming mouse (male animal), expose the heart of the Kunming mouse (male animal), observe the heart pulsation level of the Kunming mouse (male animal), cut open the right auricle of the Kunming mouse (male animal), directly insert an infusion needle into the apex of the heart of the Kunming mouse (male animal), turn on the infusion device switch, slowly and evenly inject 50 mL of normal saline into the Kunming mouse (male animal), and then slowly and evenly inject 50 mL of paraformaldehyde (4%). Dissect the whole brain of the Kunming mouse (male animal), wash the whole brain of the Kunming mouse (male animal), remove the excess part of the whole brain of the Kunming mouse (male animal), and analyze the hippocampal tissue of the Kunming mouse (male animal) by immunohistochemistry according to the basic staining process and the kit instructions to detect the protein expression level in the hippocampal tissue of the Kunming mouse (male animal).

[0087] 2.8 Determination of hippocampal gene expression

[0088] After the learning ability (latency), memory ability (swimming distance), and learning and memory retention ability (time spent in the target quadrant) of each group of Kunming mice (male animals) were measured, gene expression analysis was performed. Prepare an ice platform for dissecting Kunming mice (male animals). The operator wears protective gloves, grabs the tail of the Kunming mouse (male animal) with the right hand, and breaks the cervical vertebra of the Kunming mouse (male animal) with the left hand to execute it. Cut off the head of the Kunming mouse (male animal), remove the skin of the Kunming mouse (male animal), cut open the skull from behind the head of the Kunming mouse (male animal) to fully expose the whole brain of the Kunming mouse (male animal), clean the whole brain of the Kunming mouse (male animal), remove the redundant parts of the Kunming mouse (male animal) such as the brainstem, and effectively dissect the hippocampal tissue of the Kunming mouse (male animal) on the ice platform. Extract the mRNA of the hippocampal tissue of the Kunming mouse (male animal) and reverse transcribe it into cDNA. Design primers for the RAGE gene and internal reference gene of the Kunming mouse (male animal), add a fluorescent material (SYBR Green I) to the hippocampal tissue of the Kunming mouse (male animal), design the basic parameters of the hippocampal tissue of the Kunming mouse (male animal), perform for 2 min at 50 °C, 10 min at 95 °C, 15 s at 95 °C, and 1 min at 60 °C, and go through 45 cycles. For the hippocampal tissue of the Kunming mouse (male animal), calculate the gene expression level of the hippocampus of the Kunming mouse (male animal) according to the 2 -ΔΔCt method.

[0089] 2.9 Measurement of body weight and organ index

[0090] After the learning ability (latency), memory ability (swimming distance), and learning and memory retention ability (time spent in the target quadrant) of each group of Kunming mice (male animals) were measured, the body weight change of the Kunming mouse (male animal) was measured using an electronic balance, and the body weight data of the Kunming mouse (male animal) at 0 d, 14 d, and 28 d were analyzed and processed. At the same time, prepare an ice platform for dissecting Kunming mice (male animals). The operator wears protective gloves, grabs the tail of the Kunming mouse (male animal) with the right hand, and breaks the cervical vertebra of the Kunming mouse (male animal) with the left hand to execute it. Dissect the Kunming mouse (male animal) on the ice platform, take samples of important organs of the Kunming mouse (male animal) such as the lung, liver, kidney, and heart, clean the organ index of the Kunming mouse (male animal), and calculate the organ index of the Kunming mouse (male animal). Calculate according to the formula: The organ index (mg / g) of the Kunming mouse (male animal) = the organ mass (mg) of the Kunming mouse (male animal) / the body weight (g) of the Kunming mouse (male animal). Statistical analysis was performed on the organ index of the Kunming mouse (male animal).

[0091] 2.10 Use SPSS 19.0 software to analyze the experimental data of Kunming mice (male animals). The experimental data are expressed using and one-way ANOVA is used between the experiments of each group.

[0092] 3 Experimental Results

[0093] 3.1 Effects of the Traditional Chinese Medicine Composition on the Learning Ability of Alzheimer's Disease Kunming Mice (Male Animals)

[0094] The results showed that compared with the negative observation group, the latency of Kunming mice (male animals) in the model observation group was significantly prolonged (P < 0.05), and this comparison was statistically significant; compared with the negative observation group, the latency of Kunming mice (male animals) in the sham operation group did not change significantly (P > 0.05), and this comparison was not statistically significant; compared with the model observation group, the latency of Alzheimer's disease Kunming mice (male animals) in the positive analysis group, high-dose intervention group, and medium-dose intervention group was significantly shortened (P < 0.05), and this comparison was statistically significant; compared with the model observation group, the latency of Alzheimer's disease Kunming mice (male animals) in the low-dose intervention group did not change significantly (P > 0.05), and this comparison was not statistically significant. See Table 1, see Figure 1 (The abscissa is the group; the ordinate is the latency).

[0095] Table 1 Effects of the Traditional Chinese Medicine Composition on the Learning Ability of Alzheimer's Disease Kunming Mice (Male Animals)

[0096]

[0097] Note: Compared with the negative observation group: * P < 0.05, ** P > 0.05; compared with the model observation group: & P < 0.05, && P > 0.05

[0098] 3.2 Effects of the Traditional Chinese Medicine Composition on the Memory Ability of Alzheimer's Disease Kunming Mice (Male Animals)

[0099] The results showed that compared with the negative observation group, the swimming distance of Kunming mice (male animals) in the model observation group was significantly prolonged (P < 0.05), and this comparison was statistically significant; compared with the negative observation group, the swimming distance of Kunming mice (male animals) in the sham operation group did not change significantly (P > 0.05), and this comparison was not statistically significant; compared with the model observation group, the swimming distance of Alzheimer's disease Kunming mice (male animals) in the positive analysis group, high-dose intervention group, and medium-dose intervention group was significantly shortened (P < 0.05), and this comparison was statistically significant; compared with the model observation group, the swimming distance of Alzheimer's disease Kunming mice (male animals) in the low-dose intervention group did not change significantly (P > 0.05), and this comparison was not statistically significant. See Table 2, see Figure 2 (The abscissa is the group; the ordinate is the swimming distance).

[0100] Table 2 Effects of the Traditional Chinese Medicine Composition on the Memory Ability of Alzheimer's Kunming Mice (Male Animals)

[0101]

[0102] Note: Compared with the negative observation group: * P < 0.05, ** P > 0.05; Compared with the model observation group: & P < 0.05, && P > 0.05

[0103] 3.3 Effects of the Traditional Chinese Medicine Composition on the Learning and Memory Retention Ability of Alzheimer's Kunming Mice (Male Animals)

[0104] The results showed that compared with the negative observation group, the residence time of the model observation group of Kunming mice (male animals) in the target quadrant was significantly shortened (P < 0.05), and this comparison was statistically significant; compared with the negative observation group, the residence time of the sham operation group of Kunming mice (male animals) in the target quadrant did not change significantly (P > 0.05), and this comparison was not statistically significant; compared with the model observation group, the residence time of the positive analysis group, high-dose intervention group, and medium-dose intervention group of Alzheimer's Kunming mice (male animals) in the target quadrant was significantly prolonged (P < 0.05), and this comparison was statistically significant; compared with the model observation group, the residence time of the low-dose intervention group of Alzheimer's Kunming mice (male animals) in the target quadrant did not change significantly (P > 0.05), and this comparison was not statistically significant. See Table 3, see Figure 3 (The abscissa is the group; the ordinate is the residence time in the target quadrant).

[0105] Table 3 Effects of the Traditional Chinese Medicine Composition on the Learning and Memory Retention Ability of Alzheimer's Kunming Mice (Male Animals)

[0106]

[0107] Note: Compared with the negative observation group: * P < 0.05, ** P > 0.05 5 ; Compared with the model observation group: & P < 0.05, && P > 0.05

[0108] 3.4 Effects of the Traditional Chinese Medicine Composition on β-Amyloid Protein in the Hippocampus of Alzheimer's Kunming Mice (Male Animals) 1-40 of

[0109] The results showed that compared with the negative observation group, β-amyloid protein in the hippocampus of the model observation group of Kunming mice (male animals) 1-40The content increased significantly (P < 0.05), and this comparison was statistically significant; compared with the negative observation group, the content of β-amyloid in the hippocampus of Kunming mice (male animals) in the sham operation group 1-40 showed no obvious change (P > 0.05), and this comparison was not statistically significant; compared with the model observation group, the content of β-amyloid in the hippocampus of Alzheimer's Kunming mice (male animals) in the positive analysis group, high-dose intervention group, and medium-dose intervention group 1-40 decreased significantly (P < 0.05), and this comparison was statistically significant; compared with the model observation group, the content of β-amyloid in the hippocampus of Alzheimer's Kunming mice (male animals) in the low-dose intervention group 1-40 showed no obvious change (P > 0.05), and this comparison was not statistically significant. See Table 4, see Figure 4 (The abscissa is the group; the ordinate is β-amyloid 1-40 in the hippocampus).

[0110] Table 4 Effects of the traditional Chinese medicine composition on β-amyloid in the hippocampus of Alzheimer's Kunming mice (male animals) 1-40 Note: Compared with the negative observation group:

[0111]

[0112] P < 0.05, * P > 0.05; compared with the model observation group: ** P < 0.05, & P > 0.05 && P > 0.05

[0113] 3.5 Effects of the traditional Chinese medicine composition on IL-1β in the hippocampus of Alzheimer's Kunming mice (male animals)

[0114] The results showed that compared with the negative observation group, the content of IL-1β in the hippocampus of Kunming mice (male animals) in the model observation group increased significantly (P < 0.05), and this comparison was statistically significant; compared with the negative observation group, the content of IL-1β in the hippocampus of Kunming mice (male animals) in the sham operation group showed no obvious change (P > 0.05), and this comparison was not statistically significant; compared with the model observation group, the protein content of IL-1β in the hippocampus of Alzheimer's Kunming mice (male animals) in the positive analysis group, high-dose intervention group, and medium-dose intervention group decreased significantly (P < 0.05), and this comparison was statistically significant; compared with the model observation group, the content of IL-1β in the hippocampus of Alzheimer's Kunming mice (male animals) in the low-dose intervention group showed no obvious change (P > 0.05), and this comparison was not statistically significant. See Table 5, see Figure 5 (The abscissa is the group; the ordinate is IL-1β in the hippocampus).

[0115] Effect of the Traditional Chinese Medicine Composition on IL-1β in the Hippocampus of Alzheimer's Kunming Mice (Male Animals)

[0116]

[0117] Note: Compared with the negative observation group: * P < 0.05, ** P > 0.05; compared with the model observation group: & P < 0.05, && P > 0.05

[0118] 3.6 Effect of the Traditional Chinese Medicine Composition on IL-6 in the Hippocampus of Alzheimer's Kunming Mice (Male Animals)

[0119] The results showed that compared with the negative observation group, the content of IL-6 in the hippocampus of Kunming mice (male animals) in the model observation group increased significantly (P < 0.05), and this comparison was statistically significant; compared with the negative observation group, the change in the content of IL-6 in the hippocampus of Kunming mice (male animals) in the sham operation group was not obvious (P > 0.05), and this comparison was not statistically significant; compared with the model observation group, the content of IL-6 in the hippocampus of Alzheimer's Kunming mice (male animals) in the positive analysis group, high-dose intervention group, and medium-dose intervention group decreased significantly (P < 0.05), and this comparison was statistically significant; compared with the model observation group, the change in the content of IL-6 in the hippocampus of Alzheimer's Kunming mice (male animals) in the low-dose intervention group was not obvious (P > 0.05), and this comparison was not statistically significant. See Table 6, see Figure 6 (The abscissa is the group; the ordinate is hippocampal IL-6).

[0120] Table 6 Effect of the Traditional Chinese Medicine Composition on IL-6 in the Hippocampus of Alzheimer's Kunming Mice (Male Animals)

[0121]

[0122] Note: Compared with the negative observation group: * P < 0.05, ** P > 0.05; compared with the model observation group: & P < 0.05, && P > 0.05

[0123] 3.7 Effect of the Traditional Chinese Medicine Composition on TNF-α in the Hippocampus of Alzheimer's Kunming Mice (Male Animals)

[0124] The results showed that, compared with the negative observation group, the content of TNF-α in the hippocampus of Kunming mice (male animals) in the model observation group increased significantly (P < 0.05), and this comparison was statistically significant; compared with the negative observation group, the change in the content of TNF-α in the hippocampus of Kunming mice (male animals) in the sham operation group was not obvious (P > 0.05), and this comparison was not statistically significant; compared with the model observation group, the content of TNF-α in the hippocampus of Alzheimer's disease Kunming mice (male animals) in the positive analysis group, high-dose intervention group, and medium-dose intervention group decreased significantly (P < 0.05), and this comparison was statistically significant; compared with the model observation group, the change in the content of TNF-α in the hippocampus of Alzheimer's disease Kunming mice (male animals) in the low-dose intervention group was not obvious (P > 0.05), and this comparison was not statistically significant. See Table 7, see Figure 7 (The abscissa is the group; the ordinate is the TNF-α in the hippocampus).

[0125] Table 7 Effects of the traditional Chinese medicine composition on TNF-α in the hippocampus of Alzheimer's disease Kunming mice (male animals)

[0126]

[0127] Note: Compared with the negative observation group: * P < 0.05, ** P > 0.05; compared with the model observation group: & P < 0.05, && P > 0.05

[0128] 3.8 Effects of the traditional Chinese medicine composition on RAGE protein in the hippocampus of Alzheimer's disease Kunming mice (male animals)

[0129] The results showed that, compared with the negative observation group, the content of RAGE protein in the hippocampus of Kunming mice (male animals) in the model observation group increased significantly (P < 0.05), and this comparison was statistically significant; compared with the negative observation group, the change in the content of RAGE protein in the hippocampus of Kunming mice (male animals) in the sham operation group was not obvious (P > 0.05), and this comparison was not statistically significant; compared with the model observation group, the content of RAGE protein in the hippocampus of Alzheimer's disease Kunming mice (male animals) in the positive analysis group, high-dose intervention group, and medium-dose intervention group decreased significantly (P < 0.05), and this comparison was statistically significant; compared with the model observation group, the change in the content of RAGE protein in the hippocampus of Alzheimer's disease Kunming mice (male animals) in the low-dose intervention group was not obvious (P > 0.05), and this comparison was not statistically significant. See Table 8, see Figure 8 (The abscissa is the group; the ordinate is the RAGE protein in the hippocampus).

[0130] Table 8 Effects of the traditional Chinese medicine composition on RAGE protein in the hippocampus of Alzheimer's disease Kunming mice (male animals)

[0131]

[0132] Note: Compared with the negative observation group: * P < 0.05, ** P > 0.05; Compared with the model observation group: & P < 0.05, && P > 0.05

[0133] 3.9 Effect of the traditional Chinese medicine composition on the LRP1 protein in the hippocampus of Alzheimer's disease Kunming mice (male animals)

[0134] The results showed that compared with the negative observation group, the content of LRP1 protein in the hippocampus of Kunming mice (male animals) in the model observation group was significantly decreased (P < 0.05), and this comparison was statistically significant; compared with the negative observation group, the change in the content of LRP1 protein in the hippocampus of Kunming mice (male animals) in the sham operation group was not obvious (P > 0.05), and this comparison was not statistically significant; compared with the model observation group, the content of LRP1 protein in the hippocampus of Alzheimer's disease Kunming mice (male animals) in the positive analysis group, high-dose intervention group, and medium-dose intervention group was significantly increased (P < 0.05), and this comparison was statistically significant; compared with the model observation group, the change in the content of LRP1 protein in the hippocampus of Alzheimer's disease Kunming mice (male animals) in the low-dose intervention group was not obvious (P > 0.05), and this comparison was not statistically significant. See Table 9, see Figure 9 (The abscissa is the group; the ordinate is the LRP1 protein in the hippocampus).

[0135] Table 9 Effect of the traditional Chinese medicine composition on the LRP1 protein in the hippocampus of Alzheimer's disease Kunming mice (male animals)

[0136]

[0137] Note: Compared with the negative observation group: * P < 0.05, ** P > 0.05; Compared with the model observation group: & P < 0.05, && P > 0.05

[0138] 3.10 Effect of the traditional Chinese medicine composition on the RAGE gene in the hippocampus of Alzheimer's disease Kunming mice (male animals)

[0139] The results showed that, compared with the negative observation group, the relative expression level of the RAGE gene in the hippocampus of Kunming mice (male animals) in the model observation group increased significantly (P < 0.05), and this comparison was statistically significant; compared with the negative observation group, the change in the relative expression level of the RAGE gene in the hippocampus of Kunming mice (male animals) in the sham operation group was not obvious (P > 0.05), and this comparison was not statistically significant; compared with the model observation group, the relative expression levels of the RAGE gene in the hippocampus of Alzheimer's disease Kunming mice (male animals) in the positive analysis group, high-dose intervention group, and medium-dose intervention group decreased significantly (P < 0.05), and this comparison was statistically significant; compared with the model observation group, the change in the relative expression level of the RAGE gene in the hippocampus of Alzheimer's disease Kunming mice (male animals) in the low-dose intervention group was not obvious (P > 0.05), and this comparison was not statistically significant. See Table 10, see Figure 10 (The abscissa is the group; the ordinate is the hippocampal RAGE gene).

[0140] Table 10 Effects of the traditional Chinese medicine composition on the RAGE gene in the hippocampus of Alzheimer's disease Kunming mice (male) 2 -ΔΔCt method)

[0141]

[0142] Note: Compared with the negative observation group: * P < 0.05, ** P > 0.05; compared with the model observation group: & P < 0.05, && P > 0.05

[0143] 3.11 Effects of the traditional Chinese medicine composition on the LRP1 gene in the hippocampus of Alzheimer's disease Kunming mice (male animals)

[0144] The results showed that, compared with the negative observation group, the relative expression level of the LRP1 gene in the hippocampus of Kunming mice (male animals) in the model observation group decreased significantly (P < 0.05), and this comparison was statistically significant; compared with the negative observation group, the change in the relative expression level of the LRP1 gene in the hippocampus of Kunming mice (male animals) in the sham operation group was not obvious (P > 0.05), and this comparison was not statistically significant; compared with the model observation group, the relative expression levels of the LRP1 gene in the hippocampus of Alzheimer's disease Kunming mice (male animals) in the positive analysis group, high-dose intervention group, and medium-dose intervention group increased significantly (P < 0.05), and this comparison was statistically significant; compared with the model observation group, the change in the relative expression level of the LRP1 gene in the hippocampus of Alzheimer's disease Kunming mice (male animals) in the low-dose intervention group was not obvious (P > 0.05), and this comparison was not statistically significant. See Table 11, see Figure 11 (The abscissa is the group; the ordinate is the hippocampal LRP1 gene).

[0145] Table 11 Effects of the Traditional Chinese Medicine Composition on the LRP1 Gene in the Hippocampus of Alzheimer's Kunming Mice (Male Animals) 2 -ΔΔCt Method

[0146]

[0147] Note: Compared with the negative observation group: * P < 0.05, ** P > 0.05; Compared with the model observation group: & P < 0.05, && P > 0.05

[0148] 3.12 Effects of the Traditional Chinese Medicine Composition on the Kidney Index and Lung Index of Alzheimer's Kunming Mice (Male Animals)

[0149] The results showed that compared with the Kunming mice in the negative observation group, the changes in the kidney index and lung index of the Kunming mice in the sham operation group and the model observation group were not significant (P > 0.05), and this comparison was not statistically significant; compared with the Kunming mice in the model observation group, the changes in the kidney index and lung index of the Kunming mice (male animals) in the positive analysis group, high-dose intervention group, medium-dose intervention group, and low-dose intervention group were not significant (P > 0.05), and this comparison was not statistically significant. See Table 12, Figure 12 (The abscissa is the group; the ordinate is the kidney index and lung index).

[0150] Table 12 Effects of the Traditional Chinese Medicine Composition on the Kidney Index and Lung Index of Alzheimer's Kunming Mice (Male Animals) n = 8

[0151]

[0152] Note: Compared with the negative observation group ** P > 0.05; Compared with the model observation group: && P > 0.05

[0153] 3.13 Effects of the Traditional Chinese Medicine Composition on the Liver Index and Heart Index of Alzheimer's Kunming Mice (Male Animals)

[0154] The results showed that compared with the Kunming mice in the negative observation group, the changes in the liver index and heart index of the Kunming mice in the sham operation group and the model observation group were not significant (P > 0.05), and this comparison was not statistically significant; compared with the Kunming mice in the model observation group, the changes in the liver index and heart index of the Kunming mice (male animals) in the positive analysis group, high-dose intervention group, medium-dose intervention group, and low-dose intervention group were not significant (P > 0.05), and this comparison was not statistically significant. See Table 13, Figure 13 (The abscissa is the group; the ordinate is the liver index and heart index).

[0155] Table 13 Effects of the Traditional Chinese Medicine Composition on Liver Index and Heart Index of Alzheimer's Kunming Mice (Male Animals) n = 8)

[0156]

[0157] Note: Compared with the negative observation group: ** P > 0.05; compared with the model observation group: && P > 0.05

[0158] 3.14 Effects of the Traditional Chinese Medicine Composition on the Body Weight of Alzheimer's Kunming Mice (Male Animals)

[0159] The results showed that compared with the body weights of Kunming mice (male animals) in the negative observation group (0d, 14d, 28d), the changes in the body weights of Kunming mice (male animals) in the model observation group (0d, 14d, 28d) were not significant (P > 0.05), and this comparison was not statistically significant; compared with the body weights of Kunming mice (male animals) in the negative observation group (0d, 14d, 28d), the changes in the body weights of Kunming mice (male animals) in the sham operation group (0d, 14d, 28d) were not significant (P > 0.05), and this comparison was not statistically significant; compared with the body weights of Kunming mice (male animals) in the model observation group (0d, 14d, 28d), the changes in the body weights of Kunming mice (male animals) in the positive analysis group, high-dose intervention group, medium-dose intervention group, and low-dose intervention group (0d, 14d, 28d) were not significant (P > 0.05), and this comparison was not statistically significant. See Table 14, see Figure 14 (The abscissa is the group, and within each group, the body weights at 0d, 14d, and 28d are from left to right in sequence; the ordinate is the body weight).

[0160] Table 14 Effects of the Traditional Chinese Medicine Composition on the Body Weight of Alzheimer's Kunming Mice (Male Animals) n = 8)

[0161]

[0162] Note: Compared with the negative observation group: ** P > 0.05; compared with the model observation group: && P > 0.05

[0163] The present invention discloses a preparation method and related application research of a traditional Chinese medicine composition for the active treatment of Alzheimer's disease. The traditional Chinese medicine composition is composed of 6 Chinese medicinal materials, including 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii Maxim. var. kansuensis, 12 g of Erythrophleum fordii Oliv., 20 g of Euphorbia hirta L., 9 g of Murraya exotica L., and 7 g of Luffa cylindrica (L.) Roem. The traditional Chinese medicine composition has the main basic effects of removing dampness and promoting blood circulation to remove stasis, expelling wind and detoxifying, and promoting qi circulation and dredging collaterals.

[0164] The results of the behavioral experiments of this invention patent show that there are no significant differences in the latency, swimming distance, and residence time in the target quadrant between the observation negative group and the sham operation group. Compared with the observation negative group, there are significant differences in the latency, swimming distance, and residence time in the target quadrant of Kunming mice (male animals) in the model observation group, indicating that the animal experiment model of Alzheimer's disease has been successfully established. After treatment with high dose (18.20 g / kg), medium dose (9.10 g / kg), and low dose (4.55 g / kg) of the traditional Chinese medicine composition composed of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrina arborescens, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica, compared with the model observation group, the high dose (24.18 g / kg) and medium dose (12.09 g / kg) of the traditional Chinese medicine composition composed of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrina arborescens, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica can improve the latency, swimming distance, and residence time in the target quadrant, indicating effective treatment.

[0165] Study on hippocampal β-amyloid 1-40 The results show that the content of hippocampal β-amyloid in the brains of Kunming mice in the observation negative group and the sham operation group 1-40 is relatively low, while the content of hippocampal β-amyloid in the brains of Kunming mice in the model observation group 1-40 is relatively high. After treatment with high dose (18.20 g / kg), medium dose (9.10 g / kg), and low dose (4.55 g / kg) of the traditional Chinese medicine composition composed of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrina arborescens, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica, compared with the model observation group, the high and medium doses of the traditional Chinese medicine composition composed of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrina arborescens, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica can improve the content of hippocampal β-amyloid in the brains of Kunming mice. 1-40 indicating effective treatment.

[0166] The results of inflammatory mediators show that the content of hippocampal inflammatory mediators in the brains of Kunming mice (male animals) in the observation negative group and the sham operation group is relatively low, while the content of hippocampal inflammatory mediators in the brains of Kunming mice (male animals) in the model observation group is relatively high. After treatment with high dose (18.20 g / kg), medium dose (9.10 g / kg), and low dose (4.55 g / kg) of the traditional Chinese medicine composition composed of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrina arborescens, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica, compared with the model observation group, the high and medium doses of the traditional Chinese medicine composition composed of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii, 12 g of Erythrina arborescens, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica can improve the content of hippocampal inflammatory mediators in the brains of Kunming mice (male animals).

[0167] β-amyloid in the hippocampus of the brain 1-40 The results of the transporter showed that in the negative observation group and the sham operation group of Kunming mice (male animals), the expression of RAGE in the hippocampus of the brain tissue was down-regulated, while the expression of LRP1 was up-regulated; in the model observation group of Kunming mice, the expression of RAGE in the hippocampus of the brain tissue was up-regulated, while the expression of LRP1 was down-regulated. After treatment with the traditional Chinese medicine composition consisting of 10 g of Desmodium triflorum, 12 g of Salvia przewalskii, 12 g of Erythrina arborescens, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica at high dose (18.20 g / kg), medium dose (9.10 g / kg), and low dose (4.55 g / kg), compared with the model observation group, the high and medium doses of the traditional Chinese medicine composition consisting of 10 g of Desmodium triflorum, 12 g of Salvia przewalskii, 12 g of Erythrina arborescens, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica promoted the down-regulation of RAGE expression and the up-regulation of LRP1 expression in the hippocampus of the brain tissue of Kunming mice (male animals).

[0168] This invention patent evaluates the side effects of the traditional Chinese medicine composition consisting of 10 g of Desmodium triflorum, 12 g of Salvia przewalskii, 12 g of Erythrina arborescens, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica. The results showed that compared with the negative observation group of Kunming mice (male animals), there were no obvious changes in the organ indices and body weights of the important organs of Kunming mice (male animals) in the model observation group and the sham operation group. After treatment with the traditional Chinese medicine composition consisting of 10 g of Desmodium triflorum, 12 g of Salvia przewalskii, 12 g of Erythrina arborescens, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica at high dose (18.20 g / kg), medium dose (9.10 g / kg), and low dose (4.55 g / kg), compared with the model observation group, different doses of the traditional Chinese medicine composition consisting of 10 g of Desmodium triflorum, 12 g of Salvia przewalskii, 12 g of Erythrina arborescens, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica had no obvious effects on the organ indices and body weights of the important organs of Kunming mice (male animals). It shows that the traditional Chinese medicine composition consisting of 10 g of Desmodium triflorum, 12 g of Salvia przewalskii, 12 g of Erythrina arborescens, 20 g of Euphorbia hirta, 9 g of Murraya exotica, and 7 g of Luffa cylindrica has no side effects on Alzheimer's disease.

[0169] Comprehensive analysis shows that the present invention discloses a preparation method of a traditional Chinese medicine composition for actively treating Alzheimer's disease and related application research. The traditional Chinese medicine composition is composed of 6 Chinese medicinal materials, including 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii Maxim. var. kansuensis, 12 g of Erythrophleum fordii Oliv., 20 g of Euphorbia hirta L., 9 g of Murraya exotica L., and 7 g of Luffa cylindrica (L.) Roem. var. ovifera (L.) Roem. The traditional Chinese medicine composition has the main basic effects of removing dampness and promoting blood circulation to remove stasis, dispelling wind and detoxifying, and promoting qi circulation and dredging collaterals. Relevant animal experiments show that the high dose (18.20 g / kg) and medium dose (9.10 g / kg) of the traditional Chinese medicine composition can improve the learning ability, memory ability, learning and memory retention ability, hippocampal inflammatory mediators, β-amyloid transporter gene and protein expression of Alzheimer's disease Kunming mice (male animals). At the same time, the traditional Chinese medicine composition has no effect on the main organ indexes and related body weights of Kunming mice (male animals), indicating that the traditional Chinese medicine composition composed of 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii Maxim. var. kansuensis, 12 g of Erythrophleum fordii Oliv., 20 g of Euphorbia hirta L., 9 g of Murraya exotica L., and 7 g of Luffa cylindrica (L.) Roem. var. ovifera (L.) Roem. is effective in treating Alzheimer's disease and has no side effects.

[0170] In summary, the traditional Chinese medicine composition composed of 6 original Chinese medicinal materials, namely 10 g of Desmodium styracifolium, 12 g of Salvia przewalskii Maxim. var. kansuensis, 12 g of Erythrophleum fordii Oliv., 20 g of Euphorbia hirta L., 9 g of Murraya exotica L., and 7 g of Luffa cylindrica (L.) Roem. var. ovifera (L.) Roem., is effective in treating Alzheimer's disease and has no side effects.

[0171] Although the description of the present invention has been quite detailed and particularly describes several of the described embodiments, it is not intended to be limited to any of these details or embodiments or any particular embodiment, but rather should be regarded as providing a broad interpretation of these claims in light of the prior art by reference to the appended claims, thereby effectively covering the intended scope of the present invention. In addition, the present invention is described above with embodiments foreseeable by the inventor for the purpose of providing a useful description, and those non-substantive modifications to the present invention that are not currently foreseeable may still represent equivalent modifications of the present invention.

Claims

1. A traditional Chinese medicine composition for treating Alzheimer's disease, characterized in that, The raw materials of the traditional Chinese medicine composition and their dosages are as follows: 5-15 parts by weight of Desmodium styracifolium, 10-15 parts by weight of Salvia przewalskii Maxim. var. kansuensis, 9-15 parts by weight of Erythrophleum fordii Oliv., 8-20 parts by weight of Euphorbia hirta L., 6-12 parts by weight of Murraya exotica L., and 5-9 parts by weight of Luffa cylindrica (L.) Roem. var. hypoleuca Hand.-Mazz.

2. The traditional Chinese medicine composition according to claim 1, wherein The raw materials of the traditional Chinese medicine composition and their dosages are as follows: 10 parts by weight of Desmodium styracifolium, 12 parts by weight of Salvia przewalskii Maxim. var. kansuensis, 12 parts by weight of Erythrophleum fordii Oliv., 20 parts by weight of Euphorbia hirta L., 9 parts by weight of Murraya exotica L., and 7 parts by weight of Luffa cylindrica (L.) Roem. var. hypoleuca Hand.-Mazz.

3. A clinically suitable traditional Chinese medicine preparation for treating Alzheimer's disease, characterized in that, It is prepared by adding excipients required for formulation molding to the traditional Chinese medicine composition described in Claim 1 or 2 according to the conventional methods for preparing pharmaceutical preparations.

4. The traditional Chinese medicine preparation according to claim 3, wherein The excipients include one or more of starch, microcrystalline cellulose, sucrose, lactose, glucose, and vitamin C.

5. The traditional Chinese medicine preparation according to claim 4, characterized in that, The traditional Chinese medicine preparation is a decoction, a capsule, a pill, a granule, a tablet, or an oral liquid.

6. A method for preparing the traditional Chinese medicine composition according to claim 1 or 2, characterized in that, It includes the following steps: (1) Weigh each raw material according to the parts by weight described in Claim 1 or 2. After mixing the raw materials, add distilled water 5-15 times the total weight of the drug, soak for 1-2 hours, then decoct for 1-2.5 hours, and cool. (2) Filter the cooled medicinal liquid in step (1) with a gauze to obtain the first filtrate and the filter residue. (3) Add distilled water with the same volume as that in step (1) to the remaining drug residue in step (2), repeat steps (1) and (2) to obtain the second filtrate, and then combine and mix the first filtrate and the second filtrate to obtain the decoction of the traditional Chinese medicine composition for treating Alzheimer's disease.

7. The method according to claim 6, characterized in that, Dry the decoction obtained above at 60 °C - 80 °C for 4 d - 6 d to obtain the dry extract of the traditional Chinese medicine composition.

8. The method according to claim 7, wherein Crush, grind, and sieve the dry extract to obtain the dry powder of the traditional Chinese medicine composition.

9. The method according to claim 6, characterized in that, The filtration is carried out with a gauze, and filtration is successively carried out using 2 layers of gauze, 4 layers of gauze, and 6 layers of gauze.

10. Use of the traditional Chinese medicine composition described in Claim 1 or 2 in the preparation of a drug for treating Alzheimer's disease.

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