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New application of daphnetin in preparation of drugs for preventing and treating neurodegenerative diseases

A neurodegenerative and daphnetin technology, which is applied in nervous system diseases, drug combinations, and active ingredients of heterocyclic compounds, can solve the problems of preventing and alleviating Alzheimer's disease that have not been found.

Inactive Publication Date: 2019-06-28
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing research has not found that Daphnetin has the effect of preventing and alleviating the symptoms of Alzheimer's disease and improving cognition

Method used

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  • New application of daphnetin in preparation of drugs for preventing and treating neurodegenerative diseases
  • New application of daphnetin in preparation of drugs for preventing and treating neurodegenerative diseases
  • New application of daphnetin in preparation of drugs for preventing and treating neurodegenerative diseases

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0040] Experimental Example 1 Effect of daphnetin on the learning and memory ability of 5xFAD mice.

[0041] Animal grouping: 16 wild mice with Pd6eb background were the blank group, and 5-month-old 5xFAD mice were randomly divided into model group, huperzine A group, and daphnetin drug group. The blank group and the model group were intragastrically administered with the same volume of solvent every day; the Daphnetin drug group was 2mg / kg / day, 4mg / kg / day and 8mg / kg / day respectively. After 1 month of continuous administration, it was used for behavioral experiments.

[0042] experimental method:

[0043] 1. Y maze experiment

[0044] The Y maze is mainly used to test the working memory, discriminative learning and reference memory of animals. It consists of three identical arms, and the spatial memory ability of animals can be judged according to the order in which animals enter each arm. The mice were placed at the intersection of the three arms and explored freely for 5 ...

experiment example 2

[0048] Experimental Example 2: Effects of Daphnetin on the Morphology of Neurons in the Hippocampus of 5xFAD Mice

[0049] Animal grouping: 4 wild mice with Pd6eb background were blank group, 5xFAD mice aged 5 months were randomly divided into model group, huperzine A group, daphnetin low dose group, daphnetin middle dose group and daphnetin high dose group Dosage group, 4 rats in each group. The blank group and the model group were intragastrically given the same volume of solvent every day; the low, middle and high dose groups of Daphnetin were 2 mg / kg / day, 4 mg / kg / day and 8 mg / kg / day respectively. It was used in the experiment after continuous administration for 1 month.

[0050] experimental method:

[0051] 1. Tissue immunochemical staining

[0052]Mice were deeply anesthetized with a concentration of 4.2% chloral hydrate. Open the thorax, perfuse with 20ml of normal saline, inject 20ml of 4% paraformaldehyde after the color of the liver becomes lighter, carefully cut...

experiment example 3

[0056] Experimental Example 3: Effect of daphnetin on the content of related proteins in the hippocampus of 5xFAD mice

[0057] Animal grouping: 4 wild mice with Pd6eb background were the blank group, and 5xFAD mice aged 5 months were randomly divided into model group, huperzine A group, daphnetin low-dose group, daphnetin middle-dose group and daphnetin group In the high-dose group, there were 4 rats in each group. The blank group and the model group were intragastrically given the same volume of solvent every day; the low, middle and high dose groups of Daphnetin were 2 mg / kg / day, 4 mg / kg / day and 8 mg / kg / day respectively. It was used in the experiment after continuous administration for 1 month.

[0058] experimental method:

[0059] Determination of related proteins in the brain by Western Blot

[0060] The mice were anesthetized with chloral hydrate, and the hippocampal tissue was quickly dissected. Add RIPA lysate containing PMSF and protease phosphorylase inhibitors,...

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Abstract

The invention discloses a new application of daphnetin in preparation of drugs for preventing and treating neurodegenerative diseases, which comprises the application of daphnetin in preparation of the drugs for inhibiting beta amyloid protein aggregation in the brain. The preparation of daphnetin promotes synaptic basal release of brain neurons, and improves the application of synaptic plasticitydrugs. The application of daphnetin in preparation of drugs for improving brain cognitive impairment, the application of daphnetin in preparation of drugs for preventing and treating Alzheimer's disease. Experiments show that the daphnetin has the effects of improving cognitive impairment of 5xFAD mice, inhibiting the enzymatic activity of BACE1, promoting the enzymatic activity of TACE and ADAM17, reducing the production of A beta; and increasing the content of NMDA receptor, increasing the number of dendritic spines, increasing the content of postsynaptic protein PSD95 and enhancing synaptic plasticity, with higher clinical application value and development prospect.

Description

technical field [0001] The invention relates to a new application of daphnetin, especially a new application in the preparation of drugs for preventing and treating neurodegenerative diseases. Background technique [0002] Alzheimer's disease, commonly known as senile dementia, is a type of neurodegenerative disease that causes cognitive dysfunction caused by various factors. The pathogenesis is still unclear, and the main pathological features are amyloid plaque (Aβ) deposition, nerve fiber entanglement, massive loss of neurons, and brain atrophy. Abnormal metabolism of β-amyloid (Aβ) is an important link in the pathogenesis of AD. Under physiological conditions, the generation and clearance of Aβ in the brain are in a dynamic balance, but this balance is broken in AD patients, manifested as abnormally increased Aβ production and relatively reduced or insufficient clearance ability, leading to Aβ accumulation in the brain, which in turn triggers a A series of pathophysiol...

Claims

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Application Information

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IPC IPC(8): A61K31/37A61P25/28
Inventor 鄢黎苏薇薇罗焕敏靳雨梵
Owner SUN YAT SEN UNIV
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