CN110638823A - Application of icariin in preparation of medicine for treating vascular dementia - Google Patents
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- CN110638823A CN110638823A CN201911026216.4A CN201911026216A CN110638823A CN 110638823 A CN110638823 A CN 110638823A CN 201911026216 A CN201911026216 A CN 201911026216A CN 110638823 A CN110638823 A CN 110638823A
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Abstract
The invention discloses an application of icariin in preparing a medicament for treating vascular dementia. According to the invention, a rat VD model is established by permanently ligating bilateral common carotid arteries, the influence of icariin on VD rat nerve function and hippocampal tissue BDNF expression is observed, the relevant action mechanism of icariin in treating VD is researched, and the icariin is proved to have a definite curative effect in treating Vascular Dementia (VD), and the icariin is used for preparing corresponding medicaments and has a good clinical application prospect.
Description
Technical Field
The invention relates to application of a medicament, in particular to application of icariin in preparation of a medicament for treating vascular dementia, and belongs to the technical field of medicaments.
Background
Vascular Dementia (VD) is a neurodegenerative disease caused by abnormalities of cerebral vessels such as chronic cerebral ischemia or cerebral apoplexy for a long time, is a general term for dementia caused by various cerebrovascular diseases (ischemic, hemorrhagic and cerebral ischemic-hypoxic damage), is the second cause of senile dementia mainly manifested in the aspects of hypofunction of memory and cognition, mood change, behavior disorder and the like, and accounts for 10-50% of dementia. The mechanism is related to endothelial dysfunction, cerebrovascular injury and the like, and is particularly closely related to ischemic lesions of parts such as cerebral cortex, thalamus, hippocampus and the like. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophic factor in the central nervous system and plays a vital role in the growth, differentiation, and survival of neurons. At present, medicaments for treating vascular dementia in markets at home and abroad are mainly cholinergic medicaments, are usually mainly cholinesterase inhibitors, but the curative effect is not ideal, and no ideal specific medicament for treating the vascular dementia exists at present.
Epimedium, (academic name:Epimedium brevicornumaxim.) perennial herb, the plant height is 20-60 cm, the rhizome is thick and short, dark brown, two-time and three-time multiple leaf base and stem growth, the plant has long stem, leaflet paper or thick paper, the leaf margin has thorn teeth, the flower is white or light yellow, the flowering period is 5-6 months, the fruiting period is 6-8 months, the taste is pungent and sweet, the liver and kidney two channels walk, also known as herba epimedii, the medicine has the functions of tonifying kidney and strengthening yang, and expelling wind-damp, is commonly used for male impotence, spermatorrhea, premature ejaculation, urinary incontinence, female infertility and other diseases clinically, and the report for treating vascular dementia is not seen at present.
Disclosure of Invention
The invention aims to solve the technical problem of exploring the application of icariin in treating vascular dementia and provide a basis for researching and developing a new medicine for treating the vascular dementia.
In order to solve the technical problems, the invention provides application of icariin in preparing a medicament for treating vascular dementia.
More specifically, the invention provides an application of icariin in preparing a medicament for treating ischemic dementia diseases.
The invention also provides application of icariin in preparation of a medicine for treating Alzheimer disease.
The icariin improves and protects neuron damage by promoting the expression of BDNF mRNA and protein thereof, and plays a role in treating ischemic brain damage and aging resistance.
The icariin can also up-regulate SOD and GSH-PX activity in hippocampal tissues of the brain, down-regulate NOS activity, increase AchE and ChAT protein expression in hippocampus and improve learning and memory ability of the brain.
The icariin can also regulate Microglia (MG) through a vitamin D axis, participate in controlling the release of inflammatory factors, promote the release of endogenous neurotrophic factors and play a role in the intervention of Alzheimer's disease.
The icariin is used as the only active component and is added with pharmaceutically common auxiliary materials or auxiliary components to prepare the medicinal preparation for treating the vascular dementia.
In the application of the icariin in preparing the medicine for treating the vascular dementia, the medicine preparation for treating the vascular dementia is preferably an oral preparation.
In the application of the icariin in preparing the medicine for treating vascular dementia, the oral preparation is clinically common oral liquid, pills, granules, capsules, tablets, dropping pills or powder; the medicines of the above dosage forms can be prepared according to the conventional method of Chinese medicinal preparations.
The invention has the beneficial effects that: the invention proves that epimedium can up-regulate the level of monoamine transmitters in brain, reduce the activity of central and peripheral cholinesterase and effectively delay the aging of brain tissues through research. Icariin is the main effective component of epimedium herb, can up-regulate the activities of superoxide dismutase and glutathione peroxidase in red blood cells and liver tissues of old animals, reduce the content of lipid peroxide, and remove oxygen free radicals, thereby playing the roles of resisting oxidation, delaying senescence and the like. The invention has the contribution that the icariin is proved to have definite curative effect on treating Vascular Dementia (VD), and the icariin is used for preparing corresponding medicaments and has good clinical application prospect.
Drawings
FIG. 1 is a graph of VD rat hippocampal histopathological HE staining (× 200);
FIG. 2 is a histogram of VD rat serum BDNF level effects;
FIG. 3 is a VD graph of rat hippocampal neuronal apoptosis (x 400);
FIG. 4 is a histogram of VD rat brain tissue hippocampal neuron apoptosis rate;
FIG. 5 is a histogram of VD rat hippocampal BDNF mRNA expression effects;
FIG. 6 is a photograph of VD rat hippocampal BDNF protein expression film;
FIG. 7 is a histogram of VD rat hippocampal BDNF protein expression film gray scale values;
in the figure, 1-sham operation group, 2-model group, 3-vitamin D group, 4-icariin low dose group, 5-icariin medium dose group, and 6-icariin high dose group.
Detailed Description
The present invention will be described in further detail with reference to the following embodiments.
Example 1: the action mechanism of icariin in treating vascular dementia is disclosed. A rat VD model is established by permanently ligating bilateral common carotid arteries, the influence of icariin on VD rat nerve functions and hippocampal tissue BDNF expression is observed, and the relevant action mechanism of icariin in treating VD is researched.
Materials and instruments
1.1 male SD rat of experimental animal, SPF grade, 80, weight (170 + -20) g, purchased from the center of the third army medical laboratory animal of the liberation force, production license number: SCXK (military) 2012 and 0011.
The drug and reagent icariin (Shaanxi forest Fr natural products, Inc., batch number: SFY 161009), hematoxylin (Sigma, H9627), eosin aqueous solution (national drug group, 71014544), rabbit polyclonal antibody BDNF (Wuhan Sanying biotechnology, Inc. 25699-1-AP), and HRP-labeled goat anti-rabbit secondary antibody (Wuhan Baoshided bioengineering, Inc., BA 1054).
Main instrument microscopes (olympus BX53 biomicroscope), pathological microtomes (Leica RM2016 roller microtome, germany).
Method of producing a composite material
2.1 animal model creation and grouping 80 SD rats were randomly divided into 10 sham (i.e., control) groups and 70 VD model creation groups. Reference literature (Mao Xijing, Wang Min, in stiffness Min, etc. the influence of butylphthalide on the expression of brain-derived neurotrophic factor in CA1 region of hippocampus of rats with vascular dementia [ J]The VD rat model was replicated by the method of journal of Jilin university (medical edition), 2017, 43(5):857-－1) After general anesthesia is completed, the rat is fixed on a rat board in a supine position, and bilateral common carotid arteries are separated and permanently ligated. The sham group was only isolated but not ligated, and the remaining procedures were consistent with the VD model group. 20 deaths were due to post-operative infection, mutual bite, etc.
The rats are divided into a pseudo-operation group, a model group, a low-icariin, medium-icariin and high-dose group and a vitamin D group at random, wherein 10 rats are selected in each group. The rats in the sham operation group and the model group are administrated with 2.0 ml/(kg. d) of physiological saline for gastric lavage; the low, medium and high dose groups of icariin are respectively infused with stomach at 200mg, 400mg and 800 mg/(kg. d); the vitamin D group is intragastrically administered at a dose of 0.025 ug/(kg. D). 1 time daily, with 8 weeks of continuous drug intervention. Collecting blood without pain, centrifuging, collecting serum, and storing at-80 deg.C. Cutting off head, collecting brain tissue, washing blood with normal saline, fixing part of the blood in 4% paraformaldehyde solution, and storing part of the blood in a refrigerator at-80 deg.C.
The staining detection is carried out by fixing with 4% paraformaldehyde, embedding with paraffin section (thickness of 5 μm), staining with hematoxylin-eosin, sealing, and observing under light microscope.
And (3) detecting the BDNF level of the rat serum according to the experimental steps provided by the ELISA kit.
Observing the apoptosis of neuron cells in the hippocampal region of a rat by a method, dehydrating hippocampal tissues, clearing, waxing, embedding, slicing, baking slices and dewaxing the slices; adding protease K working solution (20 μ g/ml) dropwise, and washing with PBS for 2 times, each time for 5 min; then immersing the slices into 4% paraformaldehyde (pH7.4) solution, and fixing for 5min at room temperature; carefully absorbing the excess liquid on the glass slide by using absorbent paper, dripping 100 mu L of an Equilibration Buffer (100 mu L) on a sample area, and balancing for 5-10 min at room temperature; when the slide glass is balanced, putting the Biotinylated nucleoside mixture on ice for thawing, and preparing enough TdT enzyme reaction solution (98 mul Equisibration Buffer + 1 mul Biotinylated Nucleotide + 1 mul TdTdTenzyme) at the same time, storing the mixture on ice for later use, wherein 100 mul of reaction solution of each section is enough to cover a sample area; diluting 20 XSSC with deionized water 1: 10; soaking in 0.3% hydrogen peroxide for 3-5min to inhibit endogenous catalase, washing with PBS for 3 times, each for 5 min; adding 100 mul of Streptavidin HRP (Streptavidin horseradish peroxidase) solution to the sample, diluting the solution according to 1:500 PBS, incubating at room temperature for 30min, and washing with PBS for 3 times, 5min each time; adding 100 mu l of DAB color development liquid to the sample, developing for 30s-5min at room temperature or prolonging the color development time according to the color development condition, and finally flushing with distilled water to stop color development; and finally, observing and acquiring images of the counterstained, dehydrated, transparent and air-dried slices under a microscope.
And (3) extracting total RNA by an expression Trizol method for detecting BDNF, measuring OD260, OD280 and OD260/OD280 values by using an ultraviolet spectrophotometer, and calculating the purity and concentration of the RNA. RNA quality was estimated based on the ratio OD260/OD280, which was between 1.8 and 2.0 to meet the experimental requirements. Total RNA was reverse transcribed to cDNA and stored at-20 ℃. And (3) taking the cDNA of the reverse transcription product as a template, and adding a target gene primer and an internal reference primer for amplification. From the amplification curve data, the final data were analyzed as 2- Δ Ct. Amplification conditions pre-denaturation: at 95 ℃ for 10 min; denaturation: 95 ℃ for 15 s; annealing temperature: 60 ℃ for 15 s; extension: 72 ℃ for 35 s; the cycle was 35 times. BDNF mRNA upstream primer sequence: 5'-ATCCGAGAGCTTTGTGTGGA-3', respectively; the sequence of the downstream primer is as follows: 5'-GTGCTCAAAAGTGTCAGCCA-3', respectively; an internal reference primer beta-actin, an upstream sequence of 5'-CACGATGGAGGGGCCGGACTCATC-3'; the downstream sequence: 5'-TAAAGACCTCTATGCCAACACAGT-3' are provided.
And (3) detecting BDNF protein expression, extracting total tissue protein, centrifuging by a centrifuge, taking supernatant, and storing at-20 ℃. And calculating the protein concentration by using a regression equation according to the OD value of the protein sample. And (3) after electrophoresis gel running, membrane transfer is carried out, TBST of 5% skimmed milk powder is used for sealing for 2h, corresponding primary antibodies are added, incubation is carried out overnight at 4 ℃, TBST is fully washed for 5-6 times, corresponding HRP-labeled secondary antibodies are diluted by sealing liquid, shaking table incubation is carried out for 2h, redundant secondary antibodies are washed away, developing and fixing by fixing liquid are sequentially carried out after X-ray film pressing, the film is washed, and the gray value of the film is analyzed by Bandscan.
Analysis by statistical methods
A one-way variance test was performed using SPSS17.0,P <0.05 indicates that the statistical result is significant.
Results
3.1 the HE staining result of the pathological morphology of VD rat hippocampus tissue shows that the rat hippocampus tissue cell structure of the sham operated group is normal, is arranged orderly and has complete shape; the hippocampus of a model group rat presents diffuse injury, the number of tissue cells of the hippocampus is small, the structure is incomplete, the shape is irregular, the cell nucleus is fixed and shrunk, and the arrangement is irregular and disordered; compared with the model group, the low, middle and high icariin groups and the vitamin D group have different degrees of improvement on the damage of hippocampal tissues, the damage of neurons is reduced compared with the model group, the degeneration and necrosis of nerve cells are reduced, and the arrangement is more orderly. See fig. 1.
Effect on rat serum BDNF levels the model group rats had reduced serum BDNF levels (P) compared to the sham-operated group<0.05); the different dose icariin group has dry prognosis which is increased relative to the model group (P)<0.05). Comparison with model groups: #P＜0.05，##P＜0.01; comparison with sham group: *P＜0.05. See fig. 2.
Effect on rat hippocampal neuronal cells the apoptosis rate was increased in the model group compared to the sham operated group (P)<0.05); icariin stem prognoses a decrease in the rate of apoptosis in cells to a different extent compared to the model group. Comparison with model groups: #P＜0.05，##P＜0.01; comparison with sham group: **P＜0.01. See fig. 3, 4.
Comparing the method for detecting BDNF mRNA expression with that of the sham operation group, the BDNF mRNA expression level in the hippocampal tissue of the rat of the model group is reduced compared with that of the sham operation group, and the difference has statistical significance (P <0.05); icariin dry prognosis BDNF mRNA expression upregulation (P <0.05). Comparison with model groups: #P＜0.01; comparison with sham group: **P＜0.01. See fig. 5.
Compared with a sham operation group, the method detects that the expression level of the BDNF protein in the rat hippocampal tissue of the model group is reduced, and the difference has statistical significance (P is less than 0.05); icariin dry prognosis BDNF protein expression was up-regulated (P < 0.05). See fig. 6, 7.
Discussion of the related Art
VD is a common clinical senile disease with complex pathogenesis and unsatisfactory curative effect. With the increasing number of aging population, the problems are increased and the situation is particularly severe. The morbidity and mortality of VD in the elderly population has also increased year by year, with Alzheimer's Disease (AD) now being the first type of dementia and VD having become the second type of dementia. Researches find that the abilities of cognition, learning and memory and the like of VD patients are reduced, so that the life quality of the patients is seriously reduced, and great economic and psychological burdens are brought to families. The invention can reduce blood perfusion of a plurality of brain areas by using a permanent ligation bilateral common carotid artery rat model, particularly reduce the blood perfusion of a hippocampal area and the degeneration and necrosis of neurons caused by ischemia and hypoxia, cause the damage of nerve functions, neuroinflammation reaction and the like, and is close to the pathological characteristics and clinical manifestations of simulating human VD. BDNF is widely distributed in the central nervous system, especially in cerebral cortex, hippocampus and spinal cord. Experimental studies have found that effects of synaptic transmission and synaptic plasticity in the hippocampus are achieved by modulation of BDNF. In the development process of a nervous system, the growth, differentiation and survival of neurons are promoted, the pathological change of the neurons is improved, a certain protection effect on the damage of the neurons is achieved, and BDNF plays an important role. There is increasing evidence that BDNF plays an important role in brain development and reparative properties. It has been found that persistent ischemia-induced inflammatory responses in the hippocampal portion of the brain are one of the causative factors of vascular dementia. Dysfunction or deficiency of BDNF directly leads to learning and memory dysfunction. Therefore, trying to restore blood supply to the hippocampus is particularly important for repairing neurological function. The experimental research result of the invention shows that the VD rat BDNFmRNA and protein expression level caused by cerebral ischemia is obviously reduced. After different doses of Icariin (ICA) are dried, the expression of VD rat BDNF can be increased from protein and gene level, which shows that the icariin can play a role in improving neuron damage by up-regulating the expression of BDNF. The study of the invention proves that icariin plays a role in improving ischemic brain injury, resisting aging and the like, and can also be widely applied to the central nervous system. ICA has also been found to have a neuroprotective effect and a protective effect against cerebral ischemia-reperfusion injury. Can also improve the learning and memory ability of AD model rats caused by amyloid beta protein fragments 25-35 (Abeta 25-35) by up-regulating SOD and GSH-PX activities in hippocampal tissues and down-regulating NOS activities, increasing AchE and ChAT protein expressions in hippocampus.
In conclusion, icariin plays a role in improving and protecting neuronal damage to a certain extent by promoting expression of BDNF mRNA and protein, and shows that icariin has a definite curative effect in treating Vascular Dementia (VD), thereby providing a new research direction for future clinical medication and development and application.
Example 2: the icariin can interfere AD by regulating microglia polarization function through vitamin D axis
1. Vitamin D deficiency is ubiquitous in AD patients, and microglial modulation by the vitamin D axis plays an important role in the treatment of AD.
Vitamin D (vitamin D, Vit D) is one of the important steroid derivatives. The vitamin D axis comprises Vitamin D Receptors (VDR), vitamin D and enzymes involved in vitamin D metabolism (CYP 27B, CYP 24A). Epidemiological studies have shown that in AD patients, the Vit D deficiency phenomenon is prevalent and has a close correlation with changes in cognitive ability, while high levels of Vit D are correlated with a reduced risk of certain neurological diseases.
Vit D is available from both food and skin synthetic pathways. Its precursor Vit D3Formation of 25- (OH) D by 25-hydroxylase in the mitochondria of hepatocytes3Then the biological active 1,25(OH) is further formed through the catalytic action of 1 alpha-hydroxylase in mitochondria of proximal tubular epithelial cells2D3And plays a physiological role mainly through specific binding with a Vitamin D Receptor (VDR). VDR is present in many tissues and cells, such as the capillary endothelial cells of the brain, the prefrontal cortex, the hippocampus, and the like. Experiments have shown that 1 alpha-hydroxylase expression is present in the cerebral cortex, indicating that 1,25(OH) is produced in the central nervous system2D3。
It was found that the protective effect of Vit D on the central nervous system is mainly achieved by modulating neurotrophic factors. The contents of Nerve Growth Factor (NGF) at basal nucleus of AD patient and Brain Derived Neurotrophic Factor (BDNF) in hippocampus and apical cortex are all significantly reduced, vitamin D deficiency increases the incidence of AD, 1,25(OH)2D3Can exert protective effect on central nervous system and maintain plasticity of neurotransmission and synapse by regulating NGF, BDNF, neurotrophic factor 3(neurotrophins-3, NT-3), neurotrophic factor 4(neurotrophins-4, NT-4), glial cell line derived neurotrophic factor (GDNF) and the like, the level of NGF of the forebrain of AD patient is obviously reduced, and after autologous fibroblasts expressing human NGF by transgenosis are implanted, the cognitive evaluation grade of the patient can be improved to a certain extent. In 1 alpha-hydroxylase knockout mice, 1,25(OH)2D3Deficiency results in a decrease in NGF mRNA levels, and 1,25(OH) was supplemented2D3Can increase NGF expression in brain of APP transgenic miceSo as to achieve the purpose. The inventor of the present invention also finds that in the experiment of icariin on the rat model with vascular dementia, the BDNF mRNA level, vitamin D metabolism related enzymes (CYP 27B1, CYP24A 1) and vitamin D of the rat model group are correspondingly reduced, and the BDNF mRNA, the vitamin D metabolism related enzymes (CYP 27B1, CYP24A 1) and the vitamin D expression are up-regulated after the vitamin D and icariin are adopted.
Recent studies have shown that, in the IFN-gamma, LPS or virus infection activated MG model, high expression of proinflammatory cytokines, chemokines and effector molecules occurs, and the expression of VDR and CYP27B1 is up-regulated, and CYP27B1 is a key gene encoding 1 alpha-hydroxylase and catalyzing vitamin D to be converted into activity. Macrophages are one of the many cells that express VDR in vivo, 1,25(OH)2D3The activation of Ml type macrophages with inflammatory reaction can be promoted in the early stage, and the infiltration of the macrophages is reduced; in the later stage, macrophage differentiation to M2 type can be induced.
In conclusion, the control of the release of the inflammatory factors can be realized by directly inhibiting the over-activation of the MG, and can also enhance the response of the MG to vitamin D by up-regulating the expression of VDR receptors, inhibit the over-activation of M1 type and regulate M2 type polarization. Thus, the regulatory mechanism of the vitamin D axis for AD, in addition to promoting the release of endogenous neurotrophic factors, may also be achieved by modulating MG.
2. The understanding of traditional Chinese medicine on AD and the therapeutic effect of icariin on an AD rat model.
TCM knows AD early, and according to its main clinical manifestations, it should belong to the category of "dull disease". The disease is in the brain, involving the heart, spleen, liver and kidney, and the basic pathogenesis is kidney essence deficiency, brain marrow malnutrition and psychogenic disuse. The disease is located in the brain, kidney deficiency is the primary cause, and excess pathogenic factors are the secondary cause. Chengqingren (doctor Lin correction of errors and encephalon saying): so children with no memory are not full of brains; for those who have no memory in the high years and have become empty of brain, congenital syndrome and dementia in high years are due to insufficient brain or empty brain, so the fu-organs of Qingling are in failure to nourish. Meanwhile, the traditional Chinese medicine also considers that the kidney governs storing essence, the essence governs producing marrow, and the marrow is gathered in the brain. The brain is the marrow sea and is generated by the essence of the kidney. Nourishing marrow sea when kidney essence is abundant; the deficiency of kidney essence can not be filled into the brain, and the deficiency of brain and marrow leads to the failure of mental activities and leads to dull disease. The functions of the kidney and the brain are closely related, and the deficiency of kidney essence is an important reason for causing the deficiency of the marrow sea, so that the memory decline caused by aging can be prevented and treated through tonifying the kidney and replenishing essence, benefiting the marrow and replenishing the brain, and the effect of benefiting the brain and the brain is achieved.
The inventor of the present invention finds out in earlier research that: vitamin D is closely related to the functional concept of kidney in traditional Chinese medicine, and clearly indicates that vitamin D may be the important material basis of kidney essence storage. The action of the vitamin D endocrine system in vivo is very close to that of the kidney visceral manifestation in traditional Chinese medicine, and a plurality of intersections exist between related diseases expressed by vitamin D deficiency and the kidney essence deficiency syndrome in traditional Chinese medicine. For example: kidneys store essence and mainly grow. Vitamin D levels in neonates are generally low, which affects embryonic development and results in congenital deficiency; kidneys store essence and govern reproduction. The SD rat has the influence on the physiology and behavior of offspring due to vitamin D deficiency in pregnancy and lactation, so that the frequency and time of communication activities such as sniffing and body contact with the SD rat are reduced, and an anxiety response is generated. The model simulates the deficiency of vitamin D to cause the deficiency of kidney essence of rats by controlling sunlight and diet, and the model proves that the deficiency of vitamin D can cause the secretion disorder of animal sex hormone and show abnormal symptoms similar to the deficiency syndrome of kidney essence; kidneys store essence and govern water metabolism. In the early stages of chronic kidney disease, vitamin D is involved in 1,25(OH) with increased proteinuria2D3The FGF 23-Klotho protein system, which can improve the occurrence and development of proteinuria by modulating abnormalities in the system. Based on this, the inventor of the patent considers that the vitamin D deficiency is closely related to the kidney essence storage in the traditional Chinese medicine.
Herba Epimedii, also known as herba Epimedii, is a whole herb of Epimedium brevicornum Maxim of berberidaceae. The Shen nong Ben Cao Jing records that it has the actions of tonifying qi and strengthening will. Research shows that Icariin (ICA) is used as the main active component of epimedium herb and can improve the learning and memory capacity of AD model rats caused by amyloid beta protein fragments 25-35 (Abeta 25-35). In addition, the inventor preliminarily discusses the relevance of the vitamin D axis and the functions of storing essence and generating marrow in the kidney and proves that the vitamin D axis is related to the functions of storing essence and generating marrow in the kidney and the kidney in the traditional Chinese medicine through experimental research under the guidanceICA has the function of improving D-galactose-induced attenuation rat model serum 25(OH) D3Levels, up-regulate adrenal cortex VDR, CYP27B1, down-regulate the effects of CYP24a 1.
The Arrowsmith tool is used for discovering that the ICA has correlation with a vitamin D axis, has the effects of resisting inflammation, immunizing and the like, and discovers that the ICA regulates MG through the vitamin D axis, participates in controlling the release of inflammatory factors, promotes the release of endogenous neurotrophic factors and plays an intervention role on AD.
3. The icariin can regulate the polarization function of microglia through a vitamin D axis to achieve the effect of intervening AD.
The inventor discovers that AD rats have Vit D deficiency and Alzheimer disease and serum vitamin D are in negative correlation through preliminary experiments and literature research. Modulation of either MG or ICA intervention both alter model 1,25(OH)2D3Content and VDR expression, reduce AD pathological expression of model rats, control inflammatory factor release, reduce AD model inflammatory reaction, and are realized by directly inhibiting excessive activation of MG. Meanwhile, the vitamin D axis can also promote the release of endogenous neurotrophic factors, play a role in neuroprotection and improve the cognitive and memory abilities of rats. Based on the above recognition, the patent considers that: icariin can regulate the polarization function of microglia through a vitamin D axis to achieve the effect of intervening AD.
The embodiments of the present invention are not limited to the above-described examples, and various changes made without departing from the spirit of the present invention are within the scope of the present invention.
Claims (9)
1. Application of icariin in preparing medicine for treating vascular dementia is provided.
2. Application of icariin in preparing medicine for treating ischemic dementia diseases is provided.
3. Application of icariin in preparation of medicine for treating Alzheimer disease is provided.
4. Icariin improves and protects neuronal damage by promoting expression of BDNF mRNA and protein thereof, and plays a role in treating ischemic brain damage and aging resistance.
5. Icariin can increase AchE and ChAT protein expression in hippocampus and improve brain learning and memory ability by up-regulating SOD and GSH-PX activity in hippocampal tissues of brain and down-regulating NOS activity.
6. The icariin regulates microglia through a vitamin D axis, participates in controlling the release of inflammatory factors, promotes the release of endogenous neurotrophic factors, and plays an intervention role in Alzheimer's disease.
7. The use of icariin according to any one of claims 1 to 6 in the preparation of a medicament for the treatment of vascular dementia, wherein: icariin is used as the only active ingredient, and is added with pharmaceutically common auxiliary materials or auxiliary ingredients to prepare the medicinal preparation for treating the vascular dementia.
8. The use of icariin in the preparation of a medicament for treating vascular dementia according to claim 7, wherein: the medicinal preparation is an oral preparation.
9. The use of icariin in the preparation of a medicament for treating vascular dementia according to claim 8, wherein: the oral preparation is clinically common oral liquid, pills, granules, capsules, tablets, dripping pills or powder.
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