CN-121422010-B - Acetylcholinesterase inhibitor derived from natural products and application thereof

Abstract

The invention relates to the field of natural product pharmacy, in particular to an acetylcholinesterase inhibitor derived from natural products and application thereof. The chemical synthesis acetylcholinesterase inhibitor used in the current clinical treatment still has the problems of side effect, drug resistance and the like although achieving a certain curative effect. The invention thus provides an acetylcholinesterase inhibitor, which is a single-drug or double-drug composition derived from natural products, wherein the single-drug is ash She Fenyi flavone (TI) or Isoeugenol Acetate (IA), and the double-drug is formed by mixing TI and IA in proportion. The acetylcholinesterase inhibitor has good AChE inhibition activity, abeta aggregation resistance, oxidation resistance and good neuroprotection, and shows that TI and/or IA can be used as a novel acetylcholinesterase inhibitor for developing and using medicaments for clinically treating and/or preventing related diseases such as Alzheimer disease.

Inventors

• Wu Baixu
• ZHU MENGJIAO
• HU LIANG

Assignees

• 浙江洛兮医疗科技有限公司

Dates

Publication Date

20260505

Application Date

20251229

Claims (6)

1. 1. An acetylcholinesterase inhibitor of natural product origin, comprising an effective amount of a combination of an ash She Fenyi flavone and isoeugenol acetate, said ash She Fenyi flavone and isoeugenol acetate combination formulated at a molar ratio of ash She Fenyi flavone to isoeugenol acetate of (1-2).
2. 2. The acetylcholinesterase inhibitor according to claim 1, wherein the molar concentration of ash She Fenyi flavone is 1-4 μΜ and the molar concentration of isoeugenol acetate is 1-4 μΜ.
3. 3. The acetylcholinesterase inhibitor according to claim 1, wherein the molar concentration ratio is 1:2.
4. 4. The acetylcholinesterase inhibitor according to claim 1 or 2, wherein the optimal concentration of ash She Fenyi flavone in the ash She Fenyi flavone-isoeugenol acetate composition is 2 μΜ and the optimal concentration of isoeugenol acetate is 4 μΜ.
5. 5. Use of an acetylcholinesterase inhibitor derived from a natural product according to any one of claims 1 to 4 in the manufacture of a medicament for the prevention and/or treatment of alzheimer's disease.
6. 6. The use according to claim 5, wherein the medicament exerts a therapeutic effect by inhibiting acetylcholinesterase activity and/or inhibiting β -amyloid peptide aggregation.

Description

Acetylcholinesterase inhibitor derived from natural products and application thereof Technical Field The invention relates to the field of natural product pharmacy, in particular to an acetylcholinesterase inhibitor derived from natural products and application thereof. Background Alzheimer's Disease (AD), also known as senile dementia, is a degenerative disorder of the central nervous system that is common in the elderly. The clinical manifestations are dysmnesia, aphasia, disuse, disbelief, abstract thinking and computational impairment, personality and behavior changes, etc. With the acceleration of global aging process, the incidence of alzheimer's disease rises year by year, becoming an important factor affecting the quality of life and social burden of the elderly. At present, the pathogenesis of the disease is not completely defined, but the main hypothesis includes the beta-amyloid (Abeta) cascade hypothesis, the tau hyperphosphorylation hypothesis, the neuroinflammation hypothesis and the like. Acetylcholinesterase inhibitors (AChEI) are a major class of drugs currently used clinically to treat alzheimer's disease. It reduces the hydrolysis of acetylcholine by inhibiting the activity of acetylcholinesterase (AChE) in the body, thereby increasing the level of acetylcholine in the brain and improving the cognitive function and the ability of the patient to survive in daily life. The medicine is mainly used for treating patients with mild and moderate Alzheimer's disease, and has certain relief effect on early symptoms. However, the existing chemical synthesis of acetylcholinesterase inhibitors, such as Donepezil (Donepezil), rivastigmine (Rivastigmine) and the like, have problems of side effects, drug resistance and the like although achieving a certain curative effect. In recent years, compounds derived from natural products are continuously focused in the biomedical field, and researches find that compared with most clinical medicines, the compounds have the advantages of wide sources, various structures, small side effects and the like, and a new direction is provided for searching novel acetylcholinesterase inhibitors with low toxic and side effects and high curative effects. Disclosure of Invention The invention aims at providing an acetylcholinesterase inhibitor from natural products and application thereof. The invention provides an acetylcholinesterase inhibitor from natural products, which contains effective dose of ash She Fenyi flavone and/or isoeugenol acetate; Further, the ash She Fenyi flavone (Toxicarol Isoflavone, TI) has a structural formula shown in a formula I: I is a kind of Further, the structural formula of the isoeugenol acetate (Isoeugenyl Acetate, IA) is shown as the formula II: II (II) The CAS number of the isoeugenol acetate is 93-29-8, and the propenyl side chain (-CH=CH-CH 3) in the structure has cis-trans (Z/E) isomerism and is a cis-trans mixture of the isoeugenol acetate. The concentration of the ash She Fenyi flavone is 1-4 mu M, and the concentration of the isoeugenol acetate is 1-4 mu M; Further, the molar concentration ratio of the ash She Fenyi flavone to the isoeugenol acetate in the ash She Fenyi flavone-isoeugenol acetate composition is (1-2): 1-2; Further, the molar concentration ratio was 1:2. Further, the optimal concentration of ash She Fenyi flavone in the ash She Fenyi flavone-isoeugenol acetate composition was 2. Mu.M and the optimal concentration of isoeugenol acetate was 4. Mu.M. The invention provides a natural product-derived acetylcholinesterase inhibitor for use in: a. Preparing a medicament for preventing and/or treating AChE-related diseases; b. Preparing an anti-beta-amyloid peptide (Abeta) aggregation drug; c. preparing a medicament for preventing and/or treating diseases related to Abeta aggregation; The invention has the advantages that: the natural product-derived compound TI and/or IA provided by the invention has good AChE inhibitory activity, moderate anti-Abeta aggregation efficacy, moderate anti-oxidation activity and good neuroprotection, has no obvious cytotoxicity to human neuroblastoma cells SH-SY5Y cells, and has good biological safety, so that the TI and/or IA can be used as a novel acetylcholinesterase inhibitor for developing and using medicaments for clinically treating and/or preventing related diseases such as AD. Drawings FIG. 1 is a graph of the AChE inhibitory activity data of TI and IA compositions. FIG. 2 is a graph of data relating to the viability of SH-SY5Y cells by compounds, wherein A in FIG. 2 is the effect of TI and IA alone on the viability of SH-SY5Y cells, and B in FIG. 2 is the effect of TI and IA combination on the viability of SH-SY5Y cells. FIG. 3 is a graph of the effect of TI and IA compositions on Abeta peptide (25-35) induced cell death in SH-SY5Y cell models in vitro. Detailed Description The technical solutions described in the present invention will be clearly and completely described below with refe