CN104887659A - Application of icaritin to medicine for treating Alzheimer disease - Google Patents
Application of icaritin to medicine for treating Alzheimer disease Download PDFInfo
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- CN104887659A CN104887659A CN201510256585.8A CN201510256585A CN104887659A CN 104887659 A CN104887659 A CN 104887659A CN 201510256585 A CN201510256585 A CN 201510256585A CN 104887659 A CN104887659 A CN 104887659A
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- chromen
- trihydroxy
- enyl
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Abstract
The invention relates to an application of icaritin to a medicine for treating the Alzheimer disease. Icaritin is taken as a main raw herb, and a proper amount of auxiliary materials are added to prepare an oral preparation or an injection. By deep and detailed research of icaritin on aspects, such as a pharmacological action and an action mechanism, it is found that icaritin can obviously reduce Abeta aggregation and cholinergic nerve functional impairment, due to Abeta<25-35>, of a dementia rat model, and obviously improves the learning and memory dysfunction of the dementia rat model. Icaritin can reduce Abeta aggregation and improves the function of brain cholinergic nerve, produces a function of resisting Abeta<25-35> neurotoxicity, and obviously improves the learning and memory ability of the dementia rat model. According to the invention, by researching the effects of icaritin on the learning and memory ability, the cholinergic system, and an Abeta metabolic pathway of the dementia rat model, the pharmacological action mechanism of icaritin on treating the Alzheimer disease is illustrated, and pharmacological foundations on application of further developing icaritin are provided.
Description
Technical field
The invention belongs to medical art, the particularly application of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one in treatment alzheimer disease medicine.
Background technology
Alzheimer (Alzheimer ' s Disease, AD) be that one is common in presenium and senile gradual brain degenerative disease, main manifestations is comprehensive obstacle of acquired Premium Features, have that sickness rate is high, disability rate is high, case fatality rate high, it is the Etiological of alzheimer disease, seriously wreck the healthy of elderly population, add huge burden to family and society.Studied display in the past, the morbidity of AD may be relevant with genetic flaw, immune inflammation, metabolism disorder, cholinergic deficiency, radical damage, Neuron Apoptosis and environmental toxin etc., its pathogenetic research is mainly around expansion such as amyloid (amyloid-β, A β) cascade theory, cholinergic theory, excitotoxicity theories.Wherein, the most study of A β cascade theory, can disclose the major pathologic features of AD, comprises senile plaque (senile plaque, SP) deposition, neurofibrillary tangles (neurofibril tangle, NFT) formation and neuron loss etc.Cholinesterase inhibitor is the key agents being used for the treatment of AD at present, significantly can alleviate the symptom of AD, but can not delay the course of disease.Visible, AD pathogenesis is multifactorial, utilizes the feature of Chinese medicine multiple target effect, finds effective AD medicine significant.
Herba Epimedii abounds with in Guizhou, is conventional Chinese medicine and ethnic drug, is rich in flavone compound.Known flavone compound is a kind of natural beta-secretase inhibitor.3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one (Icartin, ICT) and icariin are all the effective ingredient extracted in Herba Epimedii, belong to flavone compound together.Have research confirm icariin to multiple AD rat model, there is preventive and therapeutic effect, its mechanism with alleviate A beta peptide aggregation and neurotoxicity relevant.ICT is one of icariin main metabolites in body, and molecular structure is significantly less than icariin, containing the chemical constitution of polyphenol hydroxyl, has the effects such as scavenging free radicals, antiinflammatory, immunosuppressant, slow down aging and neuro-protective.Research display, aβ protein core space contains some aromatic groups, and these aromatic groups can induce amyloid generation self assembly, thus forms A β fibril.Hydrophobicity effect also can induce fibril to be formed, and hydrophobic interaction can be suppressed by some micromolecular compounds containing aromatic structure.If in micromolecular compound structure on aromatic rings with hydroxyl or methoxyl group, then can form hydrogen bond with hydrogen bond donor in A beta structure-receptor combination thing, strengthen these micromolecular rejection ability, ICT possesses these physical characteristics in chemical constitution.It is reported that ICT can improve A β
25-35neuron linear mitochondrial membrane potential caused by peptide declines and nuclear damage, thus to A β
25-35the damage that peptide causes neurocyte shields.ICT, except having above effect, is also proved and has estrogen-like effects, and estrogen not only take part in the adjustment of the metabolism of APP, also can regulate the activity of neutral endopeptidase simultaneously.3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one is not also had to treat the dependent interaction research report of alzheimer disease at present.
Summary of the invention
The object of the invention is to: the application of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one in treatment alzheimer disease medicine is provided.The present invention is by studying 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one to the impact of dementia rats ability of learning and memory, cholinergic system and A β metabolic pathway, illustrate the pharmacological mechanism of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one treatment alzheimer disease, for the further Application and Development of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one medical material provides pharmacology foundation.
The present invention is formed like this: the application of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one in treatment alzheimer disease.
The application of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one in treatment alzheimer disease medicine, take 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one as crude drug, make tablet as follows: get 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one 200 ~ 2000 milligrams, sodium lauryl sulphate 0.1 ~ 0.4 milligram, starch 6 ~ 10 milligrams, microcrystalline Cellulose 60 ~ 80 milligrams, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one is mixed with starch, microcrystalline Cellulose, sieve, make it mix, add suitable quantity of water or alcohol granulation, after drying, granulate, add sodium lauryl sulphate, then with decompressor by granule tabletted, the tablet of alzheimer disease must be treated.
The application of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one in treatment alzheimer disease medicine, take 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one as crude drug, make capsule as follows: get 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one 200 ~ 2000 milligrams, sodium lauryl sulphate 0.1 ~ 0.3 milligram, starch 6 ~ 10 milligrams, microcrystalline Cellulose 60 ~ 80 milligrams, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and starch, microcrystalline Cellulose are mixed, adds ethanol in proper amount and granulate, after drying, granulate, add sodium lauryl sulphate, then add in gelatine capsule, the capsule of alzheimer disease must be treated.
The application of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one in treatment alzheimer disease medicine, is crude drug with 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, makes injection as follows: get 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one 200 ~ 2000 milligrams, add water to 1000ml, add 0.5% active carbon, keep pH value 7.0, heat micro-boiling 15 minutes, cooling, filter, add to the full amount of water for injection, fill, in 115 DEG C of sterilizings 30 minutes, cold preservation 48 hours, filters, and filtrate concentrates, spraying dry, subpackage, must treat the injection of alzheimer disease.
Described 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one is the flavone compound extracted from Herba Epimedii, molecular formula: C21H22O7, molecular weight: 386.4.
Treating a pharmaceutical agent for alzheimer disease, is take 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one as raw material, adds appropriate amount of auxiliary materials and makes oral formulations or injection.
Described pharmaceutical preparation is tablet, capsule or injection.
The applicant, by carrying out intensive research to its aspect such as pharmacological action, mechanism of action, finds that 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one can significantly alleviate A β
25-35the A beta peptide aggregation of caused dementia rats and cholinergic nerve functional lesion, and obviously improve its damage in learning and memory, main contents and the result of experimentation are as follows:
One. experiment content
A β is injected in Rats With Unilateral Hippocampus
25-35fragment makes Model of Dementia, observes 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one to the protective effect of Hippocampal Neuron Cells.
(1) ability of learning and memory of Morris determined with Morris water rat;
(2) ELISA detects the content of rat hippocampus district ACh E and ChAT;
(3) western blotting detects A β in rat hippocampus
1-40fragment Levels;
(4) statistical analysis: adopt SPSS 18.0 software to carry out statistical analysis, data with mean ± standard deviation (
± s) represent, compare between group and carry out one factor analysis of variance.
Two. experimental result
(1) compared with matched group, model group shows obvious learning and memory function and declines.After ICT treatment, rat escape latency after the treatment and detection range comparatively rat model obviously shorten, and prompting ICT can alleviate A β
25-35caused learning and memory in rats goes down.
(2) compared with matched group, in model group rats hippocampal tissue, AChE and ChAT content obviously declines.After the treatment of ICT treatment group rat oral gavage, compared with model group, AChE and ChAT content all significantly increases.
(3) compared with matched group, A β in model group rats hippocampal tissue
1-40level obviously increases.After ICT treatment, compared with model group, A β
1-40level all significantly reduces.
Three. conclusion
3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, by alleviate in brain A beta peptide aggregation and improve brain Cholinergic function of nervous system, produces anti-A β
25-35neurotoxic effect, significantly improves dementia rats ability of learning and memory.
Detailed description of the invention
Herba Epimedii has another name called Herba Epimedii, thousand liang of gold etc., is that one is pungent, sweet, warm, returns the Chinese medicine of liver, kidney channel; Be mainly used in impotence due to deficiency of the kidney, premature ejaculation of passing out semen, waist knee joint flaccidity are soft, cold extremities with aversion to cold.The object of the invention is from Herba Epimedii, to extract 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one for the treatment to senile dementia disease.
Embodiments of the invention 1: the application of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one:
Get 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one 200 ~ 2000 milligrams, sodium lauryl sulphate 0.1 ~ 0.4 milligram, starch 6 ~ 10 milligrams, microcrystalline Cellulose 60 ~ 80 milligrams, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one is mixed with starch, microcrystalline Cellulose, sieve, make it mix, add suitable quantity of water or alcohol granulation, after drying, granulate, add sodium lauryl sulphate, then with decompressor by granule tabletted, the tablet of alzheimer disease must be treated.This tablet is oral, 3 times on the one, each 1 ~ 3.
Embodiments of the invention 2: the application of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one:
Get 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one 200 ~ 2000 milligrams, sodium lauryl sulphate 0.1 ~ 0.3 milligram, starch 6 ~ 10 milligrams, microcrystalline Cellulose 60 ~ 80 milligrams, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and starch, microcrystalline Cellulose are mixed, add ethanol in proper amount to granulate, after drying, granulate, add sodium lauryl sulphate, then add in gelatine capsule, the capsule of alzheimer disease must be treated.This capsule is oral, 3 times on the one, each 1 ~ 3.
Embodiments of the invention 3: the application of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one:
Get 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one 200 ~ 2000 milligrams, add water to 1000ml, add 0.5% active carbon, keep pH value 7.0, heat micro-boiling 15 minutes, cooling, filter, add to the full amount of water for injection, fill, in 115 DEG C of sterilizings 30 minutes, cold preservation 48 hours, filtered, filtrate concentrates, spraying dry, subpackage, must treat the injection of alzheimer disease.Said preparation injection, 1 time on the one, each 10 ~ 15 milliliters.
Claims (4)
1. the application of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one in treatment alzheimer disease medicine, it is characterized in that: be crude drug with 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, make tablet as follows: get 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one 200 ~ 2000 milligrams, sodium lauryl sulphate 0.1 ~ 0.4 milligram, starch 6 ~ 10 milligrams, microcrystalline Cellulose 60 ~ 80 milligrams; Mixed with starch, microcrystalline Cellulose by 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, sieve, make it mix, add suitable quantity of water or alcohol granulation, after drying, granulate, adds sodium lauryl sulphate, then with decompressor by granule tabletted, the tablet of alzheimer disease must be treated.
2. the application of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one in treatment alzheimer disease medicine, it is characterized in that: take 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one as crude drug, make capsule as follows: get 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one 200 ~ 2000 milligrams, sodium lauryl sulphate 0.1 ~ 0.3 milligram, starch 6 ~ 10 milligrams, microcrystalline Cellulose 60 ~ 80 milligrams, 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one and starch, microcrystalline Cellulose are mixed, add ethanol in proper amount to granulate, after drying, granulate, add sodium lauryl sulphate, then pour in gelatine capsule, the capsule of alzheimer disease must be treated.
3. the application of 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one in treatment alzheimer disease medicine, is characterized in that: be crude drug with 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one, makes injection as follows: get 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one 200 ~ 2000 milligrams, add water to 1000ml, add 0.5% active carbon, keep pH value 7.0, heat micro-boiling 15 minutes, cooling, filter, add to the full amount of water for injection, fill, in 115 DEG C of sterilizings 30 minutes, cold preservation 48 hours, filters, and filtrate concentrates, spraying dry, subpackage, must treat the injection of alzheimer disease.
4., according to the application of the arbitrary described 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one of claims 1 to 3 in treatment alzheimer disease medicine, it is characterized in that: described 3,5,7-trihydroxy-2-(4-methoxy-phenyl)-8-(3-methyl-but-2-enyl)-chromen-4-one is the flavone compound extracted from Herba Epimedii, molecular formula: C21H22O7, molecular weight: 386.4.
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| CN201510256585.8A CN104887659A (en) | 2015-05-20 | 2015-05-20 | Application of icaritin to medicine for treating Alzheimer disease |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110638823A (en) * | 2019-10-25 | 2020-01-03 | 贵州中医药大学 | Application of icariin in preparation of medicine for treating vascular dementia |
| CN111544439A (en) * | 2019-02-12 | 2020-08-18 | 遵义市第一人民医院 | Application of icariin in preparation of medicine for preventing and treating Alzheimer disease |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1460482A (en) * | 2003-06-08 | 2003-12-10 | 浙江大学 | Medicine composite containing icaritin and demethylicaritin and its application |
| KR20090125973A (en) * | 2008-06-03 | 2009-12-08 | 고려대학교 산학협력단 | Composition for anti-androgenic effect |
| CN103446099A (en) * | 2013-08-19 | 2013-12-18 | 中国科学院深圳先进技术研究院 | Applications of icaritin in preparing medicament for preventing and treating alzheimer disease |
-
2015
- 2015-05-20 CN CN201510256585.8A patent/CN104887659A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1460482A (en) * | 2003-06-08 | 2003-12-10 | 浙江大学 | Medicine composite containing icaritin and demethylicaritin and its application |
| KR20090125973A (en) * | 2008-06-03 | 2009-12-08 | 고려대학교 산학협력단 | Composition for anti-androgenic effect |
| CN103446099A (en) * | 2013-08-19 | 2013-12-18 | 中国科学院深圳先进技术研究院 | Applications of icaritin in preparing medicament for preventing and treating alzheimer disease |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111544439A (en) * | 2019-02-12 | 2020-08-18 | 遵义市第一人民医院 | Application of icariin in preparation of medicine for preventing and treating Alzheimer disease |
| CN110638823A (en) * | 2019-10-25 | 2020-01-03 | 贵州中医药大学 | Application of icariin in preparation of medicine for treating vascular dementia |
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