Application of kaempferol or composition containing kaempferol in preparation of medicine for treating and / or relieving multiple sclerosis

Abstract

An EAE mouse model proves that the kaempferol and the ephedra, radix aconiti carmichaeli and herba asari particles can obviously save the myelin sheath damage of a mouse. Meanwhile, through serum metabolome analysis and metabolome and transcriptome analysis, the binding force of kaempferol and MMP3 is predicted, and through an EAE mouse model, it is proved that kaempferol can reduce expression of MMP3 through binding with MMP3, and IL-17 and demyelination are inhibited, so that the disease progression of EAE is delayed. Therefore, the invention proves that the kaempferol and the ephedra, monkshood and asarum granules can be used for treating and / or relieving the multiple sclerosis (MS), and the invention provides a new way for the treatment of the multiple sclerosis (MS).

Description

Technical Field

[0001] The invention belongs to the field of medicine, and particularly relates to the application of kaempferol or a composition containing kaempferol in preparing a drug for treating and / or alleviating multiple sclerosis. Background Art

[0002] Multiple sclerosis (MS) is an immune and chronic inflammatory disease of the central nervous system (CNS), affecting approximately 2.3 million people worldwide. The disease seriously reduces the quality of life of patients and causes a serious financial burden. It is a global public health problem that seriously threatens human health. Its pathogenesis is characterized by white matter demyelination, astrocyte proliferation, microglial activation and axonal damage, leading to loss of motor, sensory and cognitive functions and progressive neurological dysfunction. The etiology and pathogenesis have not yet been fully clarified.

[0003] In order to develop safer and more effective treatments, people are working to explore the molecular mechanisms of MS and develop drugs targeting these pathways. Animal models are the key to solving the pathogenesis of MS. The three most characteristic animal models of MS are: (1) experimental autoimmune / allergic encephalomyelitis (EAE); (2) virus-induced chronic demyelinating disease, namely murine encephalomyelitis virus (TMEV) infection; (3) toxin-induced demyelination.

[0004] Matrix Metalloproteinase-3 (MMP3) amino acid binding sites refer to specific amino acid residue positions in the MMP3 protein structure that are involved in substrate binding and activity regulation. As a protease, MMP3 needs to bind to substrates and perform catalytic activity at specific amino acid residues. MMP-3 is present in dopaminergic neurons, where it can be activated intracellularly by the serine protease HtrA2 / Omi. Upregulation of MMP-3 in central nervous system pathologies has shown its role in several neurodegenerative diseases. Dysregulated MMP-3 activity appears to aggravate many neurodegenerative diseases by disrupting the blood-brain barrier, promoting demyelination and apoptosis, or causing additional inflammatory responses. In the pathological brain, MMP-3 is expressed in damaged neurons, oligodendrocytes, astrocytes, pericytes, and reactive microglia / macrophages. After CNS ischemia, trauma, or infection, inflammatory mediators, such as tumor necrosis factor-α and interleukin-1β, induce transcription factors activator protein-1 and nuclear factor-κB, which subsequently bind to similar sites in the MMP-3 promoter region of activated microglia, thereby inducing MMP-3 pro-transcription.

[0005] MMP-3 is also associated with multiple sclerosis and demyelination. In a mouse model of spontaneous demyelination, MMP-3 can degrade myelin basic protein and is upregulated in the brain before the onset of the disease. In addition, the expression of MMP-3 is observed inside and around the lesions and in the blood of patients with multiple sclerosis. MMP3 has been shown to regulate the activities of other MMPs and cytokines involved in the inflammatory response of MS, and its dysregulation can lead to the destruction of myelin (the protective sheath around nerve fibers), resulting in the characteristic symptoms of MS, such as visual impairment, muscle weakness, and cognitive deficits. The exact mechanism of the relationship between MMP3 and MS is still under investigation, but targeting MMP3 activity has been proposed as a potential therapeutic strategy for treating MS inflammation and neurodegeneration, yet the specific mechanism has not been reported.

[0006] The IL-17 pathway indeed plays an important role in the immune-inflammatory response of multiple sclerosis. IL-17 is an inflammatory cytokine, and its overactivation is closely related to the onset and disease progression of multiple sclerosis. IL-17 triggers neuronal damage and demyelination by promoting the infiltration of inflammatory cells and the activation of immune cells, exacerbating the pathological changes of multiple sclerosis. Therefore, the regulation of the IL-17 pathway has become one of the important strategies for treating multiple sclerosis.

[0007] There is no clear record of MS in traditional Chinese medicine literature. Most are named differently according to the manifestations in different stages of the disease. Those mainly manifested by limited movement should be named "flaccidity syndrome", those mainly manifested by dizziness should be named "vertigo", and "dim and hazy vision" is mostly named for those mainly manifested by visual impairment. "Hidden paralysis" generally refers to difficulty walking accompanied by slurred speech, and those manifested by abnormal gait such as swaying from side to side should be named "bone flaccidity". Professor Zhang Qiucai treated MS with the principle of warming yang, replenishing qi, and dredging meridians, and formulated prescriptions with aconite, ephedra, etc., achieving good results. Zhao Xuesong et al. believed that based on its clinical manifestations, MS should be named "bone flaccidity", and treating this disease with a prescription for tonifying the kidney and replenishing the marrow also had effects; Niu Lei proposed that when introducing the diagnosis and treatment experience of Professor Zheng Shaozhou, those manifested by flaccidity of tendons and bones should be named "flaccidity of tendons and bones", and treating this disease with methods of tonifying the liver and kidney and strengthening the primordial qi. Zhou Zheyi et al. believed that the main syndromes of MS were liver-kidney yin deficiency, spleen-kidney yang deficiency, blood stasis, etc., and thought that it might be related to the consumption of yin fluid, damage to kidney yin, and subsequent series of changes.

[0008] Precisely because the etiology of MS is not yet clear, there are very few effective treatment options for patients with secondary progressive and primary progressive multiple sclerosis. There are various effective disease-modifying treatments for relapsing-remitting MS, but none of them have achieved a curative effect. Therefore, it is very urgent to explore new pathogenic mechanisms and treatment methods for MS. Summary of the Invention

[0009] The present invention is based on the effective ingredients of Ma Huang Fu Zi Xi Xin Tang, a representative prescription for treating Shao Yin disease, and conducts in-depth exploration on whether it can target MMP3 to regulate the IL-17 pathway to inhibit spinal cord demyelination and improve nerve damage in multiple sclerosis models. It is found that kaempferol or a pharmaceutical composition containing kaempferol has obvious therapeutic effects in treating and / or alleviating multiple sclerosis, which provides a new approach for the treatment of multiple sclerosis (MS).

[0010] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions.

[0011] The present invention provides the use of kaempferol or a composition containing kaempferol in preparing a drug for treating and / or alleviating multiple sclerosis, wherein kaempferol is a main active ingredient in the composition.

[0012] In certain embodiments, the medicament further comprises a pharmaceutically acceptable carrier.

[0013] In certain embodiments, the kaempferol and the pharmaceutically acceptable carrier are prepared into a kaempferol preparation.

[0014] In certain embodiments, the dosage form of the kaempferol preparation is any one of tablets, capsules, granules, suspensions, or syrups.

[0015] In certain embodiments, the amount of kaempferol is 20-40 mg / kg, preferably 30-40 mg / kg, and more preferably 30 mg / kg.

[0016] In certain embodiments, the composition containing kaempferol is a traditional Chinese medicine composition, which consists of ephedra, aconite and asarum, preferably Ma Huang Fu Zi Xi Xin Tang or Ma Huang Fu Zi Xi Xin granules.

[0017] In certain embodiments, the weight ratio of ephedra, aconite root and asarum is (1-2):(2-3):(1-2). Preferably, the weight ratio of ephedra, aconite root and asarum is 1:1:1.

[0018] In certain embodiments, the kaempferol is used as the sole active ingredient in the preparation of a drug for treating and / or alleviating multiple sclerosis.

[0019] The present invention, relative to the prior art, proves that kaempferol and ephedra aconite asarum granules can significantly save the myelin destruction of mice through EAE mouse model. Meanwhile, through serum metabolome analysis and metabolome and transcriptome analysis, the binding force of kaempferol and MMP3 is predicted, and kaempferol is proved to reduce the expression of MMP3 by combining with MMP3 through EAE mouse model, and IL-17 and demyelination are inhibited to delay the progression of EAE disease. Therefore, the present invention proves that kaempferol and ephedra aconite asarum granules can treat and / or alleviate multiple sclerosis (MS), and the present invention provides a new approach for the treatment of multiple sclerosis (MS). BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 These are the results of component analysis of Ma Huang Fu Zi Xixin Granules; among them, Figure A is Ma Huang Fu Zi Xixin Granules, Figure B is a schematic diagram of component analysis of Ma Huang Fu Zi Xixin Granules, Figure C is a mass spectrometry analysis total ion current graph in positive ion mode, Figure D is a mass spectrometry analysis total ion current graph in negative ion mode, and Figure E is the medicinal components of Ma Huang Fu Zi Xixin Granules.

[0021] Figure 2 These are the results of MFX alleviating the disease development of the EAE model; Figure A shows the modeling process of EAE model mice, Figure B shows the behavioral test results, Figures C and D show the serum and spinal cord autophagy and inflammation indicators, and Figure E shows the results of LFB staining, HE staining and electron microscopy.

[0022] Figure 3 Figure 1 shows the results of the metabolomics analysis of blood components of MFX-containing serum; Figure A shows the experimental process, Figure B shows the statistics of significantly different metabolites, Figure C shows the multi-peak diagram of MRM metabolite detection, Figure D shows the classification diagram of differential metabolites, and Figure E shows the correlation analysis between Flavnoids and the other five types of blood components.

[0023] Figure 4 The results of MFX transcriptomic analysis; Figure A is a statistical diagram of significantly differentially expressed genes, Figure B is a cluster analysis diagram of differentially expressed genes after normalization, Figures C and D are correlation analyses of differentially expressed genes and signaling pathways, and Figure E is a ridge diagram of signaling pathway enrichment analysis.

[0024] Figure 5 Figure 3 is the result of the joint analysis of the MFX metabolome and transcriptome; Figure A is the correlation result between differential genes and enriched pathways, Figure B is a nine-quadrant diagram of the relationship between signal pathways and differential genes and metabolites, Figure C is a heat map of the joint analysis of differential genes and differential metabolites, Figure D is an analysis of metabolite types, Figure E is an immunofluorescence co-localization map of MMP3 in neurons, and Figure F is a molecular docking map of MMP3 and kaempferol.

[0025] Figure 6 These are the results of kaempferol treatment of multiple sclerosis after in vivo knockout of the MMP3 gene; Figure A is a schematic diagram of the MMP3-shRNA intrathecal injection model, Figures BC are the results of immunoblotting, Figure D is the behavioral results after knocking down MMP3, Figure EF is immunofluorescence detection of spinal cord sections, and Figure GI is the results of LFB staining, HE staining and electron microscopy. DETAILED DESCRIPTION

[0026] The present invention will be further described below in conjunction with specific embodiments, and the advantages and features of the present invention will become clearer as the description proceeds. However, these embodiments are exemplary only and do not constitute any limitation to the scope of the present invention. It should be understood by those skilled in the art that the details and forms of the present invention may be modified or replaced without departing from the spirit and scope of the present invention, but these modifications and replacements all fall within the scope of protection of the present invention.

[0027] Example 1 Analysis of ingredients in Ma Huang Fu Zi Xi Xin granules

[0028] To ensure the repeatability of the experiment, the study used Chinese medicine granules (MFX) from Guangdong Yifang Pharmaceutical Co., Ltd., where 1 gram of Radix Aconiti Lateralis Preparata granules is equivalent to 8.3 grams of herbal medicine, 1 gram of Asarum granules is equivalent to 3.3 grams of herbal medicine, and 1 gram of Ephedra granules is equivalent to 5 grams of herbal medicine. The detected substances were analyzed for OB (oral availability) using TCMSP (https: / / old.tcmsp-e.com / tcmsp.ph), and active substances were screened using OB>30 and DL>0.18.

[0029] The analysis results are as follows Figure 1 As shown, the Mahuangfuzixixin compound granules are composed of three granules ( Figure 1 A) Ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS / MS) was used to accurately identify and quantify the compound granules ( Figure 1 B), for the mixed sample quality control, the total ion current (TIC) of the QC sample is obtained, i.e., the sum of the intensities of all ions in the mass spectrum at each time point is plotted against time, and the ordinate is the ion current intensity of the ion detection (intensity unit is cps, countper second) ( Figure 1 C and D), component analysis results ( Figure 1 E). The results of component analysis show that it can be divided into six categories: Alkaloids, Flavonoids, Lignans and Coumarins, Phenolic acids, Tannins and Terpenoids. The specific monomers are as follows: Figure 1E. Among them, there are 19 flavonoids accounting for 48.7%, 7 phenolic acids accounting for 17.9%, 5 lignans and coumarins accounting for 12.8%, 4 terpenoids accounting for 10.2%, 2 tannins accounting for 5.1%, and 2 others accounting for 5.1%.

[0030] Example 2 Ma Huang Fu Zi Xi Xin Granules can delay the aggravation of autoimmune encephalomyelitis (EAE)

[0031] EAE model was established in C57 mice: MOG 35-55 antigen was diluted to a concentration of 5 mg / ml with saline, and an equal volume of CFA was added at a ratio of 1:1. Mycobacterium tuberculosis H37Ra was then added to a final concentration of 4 mg / ml, and the mixture was thoroughly emulsified. Each C57BL / 6 mouse was subcutaneously injected with 0.1 ml at 4 points on both sides of the spine, and PTX (500 ng / mouse) was intraperitoneally injected at 0 h and 48 h (as Figure 2 As shown in A). Starting from the day of immunization, the neurological function evaluation of experimental mice follows the internationally recognized five-point standard: no symptoms (0 points), loss of tail tension (1 point), hind limb weakness (2 points), hind limb paralysis (3 points), hind limb and forelimb paralysis (4 points), dying / death (5 points). When the clinical symptoms fall between two scores, the lower score is increased by 0.5 points.

[0032] C57BL / 6 mice were divided into control group, model group and MFX high, medium and low dose groups. The low, medium and high concentrations of MFX were: 0.2g / ml, 0.4g / ml and 0.8g / ml. 2ml was given by intragastric administration each time. Ma Huang Fu Zi Xixin Decoction was given by intragastric administration for 14 days for further analysis.

[0033] After administration of high-concentration MFX (0.8 g / ml), the clinical score was lower than that of the model group, and no significant difference was found between the low-dose and medium-dose groups and the model group ( Figure 2 B). At the same time, the serum and cerebrospinal fluid of EAE mice were tested and it was found that the level of inflammatory factor TNF-α in the high-dose MFX group was lower than that in the model group, but higher than that in the normal group ( Figure 2 C and D).

[0034] Luxol fast blue (LFB) is a copper-phthalocyanine dye that has the staining properties of myelin phospholipid structure in alcohol solution. LFB myelin staining can well show the myelin structure of nerve tissue. If the myelin sheath is diseased, the number of myelin sheaths will be significantly reduced or disappeared during staining, or the myelin sheath morphology will be irregular. Figure 2As shown in E, the LFB staining in the model group was the lightest, and the MFX high-dose group recovered to a dark color, indicating that high-dose MFX particles can protect the myelin sheath and prevent demyelination. HE staining results showed that there were different degrees of spinal cord inflammatory infiltration after modeling, among which the model group had the highest intensity. The HE staining results of the MFX high-dose group showed that the level of inflammatory infiltration was higher than that of the control group, but the degree was the lightest among all the modeling groups. Transmission electron microscopy imaging showed that the myelin structure of EAE mice was loose after modeling, and the myelin density or thickness was reduced, while the myelin damage in the MFX high-dose group was significantly rescued.

[0035] Example 3 Analysis of blood components of Mahuangfuzixixin granules

[0036] The model mice were gavaged with high concentrations of MFX for 5 days, twice a day. Blood samples were drawn from the animals two hours after the last gavage on the fifth day. Ten mice were prepared for each group. Blood was collected using anticoagulation tubes, gently mixed and centrifuged (e.g., 3000 rpm, 10 minutes) to separate plasma. The plasma was transferred to an RNase-free tube and immediately subjected to metabolomics analysis using high-performance liquid chromatography (HPLC) and mass spectrometry (MS). PBMCs were separated using gradient centrifugation (such as Ficoll density gradient centrifugation). The isolated PBMCs were collected and washed with PBS, followed by cell counting, RNA extraction, library construction based on RNA quality, and sequencing using the high-throughput sequencing platform Illumina for transcriptomics analysis. Figure 3 As shown in A, metabolomics analysis of MFX-containing serum was performed, and a total of 41 up-regulated and 173 down-regulated metabolites were screened out ( Figure 3 B). The multi-peak diagram of MRM metabolite detection (ion current spectrum of multi-substance extraction, XIC) showed that the differential metabolites were divided into 6 categories, among which flavonoids were the most abundant ( Figure 3 D), flavonoids have the strongest correlation with the other five types of blood components ( Figure 3 E).

[0037] Example 4 Transcriptomic Analysis of Ma Huang Fu Zi Xi Xin Granules

[0038] Peripheral blood mononuclear cells (PBMCs) were extracted from drug-containing plasma for transcriptomic analysis of blood components. The results showed that there were 14 significantly upregulated genes and 10 significantly downregulated genes ( Figure 4 A). In order to study the expression patterns of genes under different treatment conditions, first, all differentially expressed genes were normalized and then clustered. The results showed that the clustering of the control group and the treatment group was opposite ( Figure 4B). The differentially expressed genes were enriched into signal pathways, and TNF-α and IL-17 signal pathways related to autoimmune diseases were found in the 50 differentially expressed gene-related signal pathways. Correlation analysis between differentially expressed genes and signal pathways was performed ( Figure 4 C and D). Select the 20 GSEA enrichment items with the smallest qvalue and draw the enrichment analysis ridge plot, showing that the TNF pathway is inhibited ( Figure 4 E).

[0039] Example 5 Combined metabolomic and transcriptomic analysis and in vivo validation of Mahuangfuzixixin granules

[0040] Using immunofluorescence method, spinal cord tissue paraffin sections were taken, MMP3 protein was stained with green fluorescence, GFAP (astrocytes), NeuN (neurons) and IBA1 (microglia) were stained with red fluorescence to represent different nerve cells. Fluorescence inverted microscope was used to observe the localization of MMP3 in nerve cells. AutoDock was used to simulate the docking of MMP3 protein and kaempferol molecule.

[0041] Figure 5 A is the correlation result between differentially expressed genes and enriched pathways, showing that the down-regulated MMP3 gene is correlated with the TNF signaling pathway and the IL-17 signaling pathway. Subsequently, the relationship between the signaling pathway and the differentially expressed genes and metabolites is shown through a nine-quadrant diagram ( Figure 5 B). The combined analysis of differentially expressed genes and differentially expressed metabolites revealed that differences in quercetin, luteolin, and kaempferol all belong to the class of flavonoids. Using EAE model mice (in vivo experiments) to detect the localization of MMP3 and nerve cells, it was found that MMP3 was most highly expressed in neurons. The binding ability of kaempferol to MMP3 was predicted, showing that the two had a strong binding ability ( Figure 5 .F).

[0042] Example 6 Kaempferol treatment of multiple sclerosis depends on MMP3 protein

[0043] The packaged MMP3-shRNA adenovirus solution was injected intrathecally (IT) into EAE mice (clinical symptoms of each group of mice were ≥1.0 since the onset of EAE). The treatment groups were set up for 1 week and 2 weeks. After sampling, the expression of MMP3 was detected by western blot and QPCR to determine the successful mutation of the 2-week group. The purpose of intrathecal injection is to inject the drug into the subarachnoid space to allow it to spread in the cerebrospinal fluid (CSF). Injecting AAV viral vectors into the cerebrospinal fluid can achieve extensive gene transduction throughout the central nervous system. Steps for intrathecal injection of AAV mice: ① Add 5ul of local anesthetic (20% Licardoine hydrochloride) to 95ul of ultra-purified AAV virus solution, and use a gun tip to gently blow and mix. Place on ice for temporary storage (8ul can be injected per mouse). ② Use a 27G needle to absorb 8ul of injection solution, and be careful to remove bubbles. After disinfecting the clean bench with 75% ethanol, the mouse is placed with its back facing up. Grasp the ilium of the mouse with the thumb and index / middle finger of the non-dominant hand and fix the mouse on the surgical board in the clean bench. Cover the upper body of the mouse with sterile gauze or towel to keep it cool. After grasping the mouse, keep the skin tension on the back of the mouse between the thumb and index finger. Shave and disinfect the skin of the back injection area. Use the thumb or index finger of the dominant hand to feel the intervertebral space at the midline of the bilateral ilium, and press the indentation with the fingernail to indicate the intervertebral space of L5-L6 as the injection position. Slightly rotate the base of the tail to indicate the midline of the spine. Adjust the bevel of the needle to point it toward the animal's head before injection. ③ Make sure the animal is firmly fixed and align the needle along the midline of the spine. Gently insert the needle vertically (or slightly tilted 70-80°) into the intersection of the indentation, and keep the syringe vertical. When touching the bone, slowly reduce the angle to about 30°, and then slide the needle into the intervertebral space. ④ Push the AAV injection solution at a rate of 4s / μl per time. After injection, the needle was kept in place for about 1 minute, and then the needle was gently rotated and pulled out to avoid leakage. ⑤ After the injection was completed, the activity function of the mouse limbs was immediately evaluated, 0 points, no limb weakness; 1 point, slight weakness of the hind limbs, no gait abnormality; 14 days after intrathecal injection, the control group was given normal saline, and the treatment group was gavaged with kaempferol for 7 days before the samples were collected. Figure 6 A is a schematic diagram of MMP3-shRNA intrathecal injection modeling. When EAE modeling caused an increase in MMP3 and IL-17, the results of immunoblotting showed that MFX could reduce the levels of MMP3 and IL-17 proteins, and IL-17 was positively correlated with MMP3. When MMP3 protein was knocked out, MFX could not reduce the level of IL-17 ( Figure 6 C).

[0044] When EAE was treated with kaempferol, clinical scores were reduced, and when MMP3-shRNA was knocked down, MMP3 levels were reduced but IL-17 was increased ( Figure 6 D). Immunofluorescence detection of spinal cord sections showed that both MMP3 and IL-17 were elevated in the EAE model. When MFX or kaempferol was used, the protein levels of MMP3 and IL-17 were reduced. However, knocking down MMP3 did not cause IL-17 in neurons to reduce MMP3. After EAE modeling, the number of myelin sheaths was significantly reduced or disappeared, or the myelin sheath morphology was irregular when LBF staining was performed. At the same time, the LFB staining in the model group was the lightest, and the MFX high-dose group and Kaempferol restored the dark color, indicating that high-dose MFX particles can protect the myelin sheath and prevent demyelination. When MMP3 was knocked down and kaempferol was used at the same time, no improvement was seen (such as Figure 6 G). HE staining results showed that there were different degrees of spinal cord inflammatory infiltration after modeling, among which the model group had the highest intensity. The HE staining results of the MFX high-dose group and the kaempferol group showed higher levels of inflammatory infiltration than the control group, but the degree was the lightest among the modeling groups (such as Figure 6 H), when knocking down MMP3 and using Kaempferol simultaneously, no improvement in inflammatory infiltration was observed. Transmission electron microscopy imaging showed that the myelin structure of EAE mice was loose after modeling, and the density or thickness of myelin was reduced, while the demyelination in the high-dose MFX group and the kaempferol group was significantly rescued (e.g. Figure 6 I).

[0045] Therefore, it can be seen that kaempferol in MFX reduces the expression of MMP3 by binding to MMP3, and inhibits IL-17 and demyelination, thereby delaying the progression of EAE.

[0046] Unless otherwise specifically stated, the numerical value set forth in these embodiments does not limit the scope of the present invention. In all examples shown and described here, unless otherwise specified, any specific value should be interpreted as merely exemplary, rather than as restriction, and therefore, other examples of exemplary embodiments may have different values.

Claims

1. Use of kaempferol or a composition containing kaempferol in the preparation of a drug for treating and / or alleviating multiple sclerosis, wherein kaempferol is a main active ingredient in the composition.

2. The use according to claim 1, characterized in that: The medicament further includes a pharmaceutically acceptable carrier.

3. The use according to claim 2, characterized in that: The dosage form of the drug is any one of tablets, capsules, granules, suspensions, emulsions, solutions, syrups, decoctions or injections.

4. The use according to claim 1, characterized in that: The dosage of kaempferol is 20-40 mg / kg, preferably 30-40 mg / kg, more preferably 30 mg / kg.

5. The use according to claim 1, characterized in that: The composition containing kaempferol is a traditional Chinese medicine composition, which consists of ephedra, aconite and asarum.

6. The use according to claim 5, characterized in that: The mass fractions of the ephedra, aconite and asarum are (1-2):(2-3):(1-2).

7. The use according to claim 6, characterized in that: The mass proportions of ephedra, aconite root and asarum are 1:1:1.

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