Application of xanthohumol to inhibition of abnormal aggregation of Tau proteins

A technology of xanthohumol and protein, applied in the field of biomedicine, can solve the problems of unsatisfactory drug efficacy, achieve the effect of less toxic and side effects, good curative effect, and inhibit abnormal aggregation of Tau protein

Inactive Publication Date: 2019-03-08
SHENZHEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to overcome the above-mentioned deficiencies in the prior art, and provide a kind of xanthohumol as an inhibitor of abnormal aggregation of Tau protein or the application in medicine, so as to solve the clinical problems of existing drugs for inhibiting abnormal aggregation of Tau protein and treating tau protein disease. Technical problems of unsatisfactory efficacy of traditional Chinese medicine

Method used

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  • Application of xanthohumol to inhibition of abnormal aggregation of Tau proteins
  • Application of xanthohumol to inhibition of abnormal aggregation of Tau proteins
  • Application of xanthohumol to inhibition of abnormal aggregation of Tau proteins

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1: Inhibitory effect of different concentrations of xanthohumol on TauK18 protein fibrosis.

[0047] Because heparin sodium induces TauK18 protein to self-aggregate to form fibers. In order to simulate abnormal aggregation of Tau protein in the brain to form neurofibrillary tangles, in this embodiment, TauK18 protein was induced by heparin sodium to form abnormal aggregation to form neurofibrillary tangles. Thioflavin T (ThT) can interact with the β-sheet in the aggregated filaments to generate fluorescence, and its fluorescence intensity is positively correlated with the amount of fiber, which can be used for quantitative analysis of protein fiber amount.

[0048] Method: The purified TauK18 protein freeze-dried product was obtained, accurately weighed, dissolved in Tris-HCl Buffer (pH7.4), and prepared into a protein mother solution of about 0.56 mg / mL, then quantified by BCA, and recorded the exact concentration. Accurately weigh xanthohumol, prepare high-co...

Embodiment 2

[0056] Example 2: Transmission electron microscope experiment of xanthohumol inhibiting TauK18 protein fibrosis

[0057] Methods: The aggregation and fibrosis of TauK18 treated with different concentrations of xanthohumol can be visually observed by transmission electron microscopy (TEM), which is a strong evidence for the ThT fluorescence experiment. From the ThT experiment of embodiment 1, collect respectively 5 μ L of the sample of DMSO control group, low concentration xanthohumol group (1 μ M), medium concentration xanthohumol group (10 μ M) and high concentration xanthohumol group (50 μ M), dilute Then drop it onto the copper grid, settle for 0.5 hours, then absorb the excess sample with filter paper, then drop 5 μL of 3% uranyl acetate respectively, let it stand for 2 minutes, and then absorb the excess uranyl acetate with filter paper. Place in a transmission electron microscope (NIPPON TEKNO, JEM-1230), observe at an accelerating voltage of 100kV, take pictures and sav...

Embodiment 3

[0059] Embodiment 3: The depolymerization effect of xanthohumol on TauK18 protein fiber

[0060] Example 3 further verifies that xanthohumol has depolymerization effect on TauK18 fibers.

[0061] Method: Add different concentrations of xanthohumol to the reaction system that has formed fibers to explore the depolymerization effect of xanthohumol on TauK18 fibers. Around the 19th hour of the fibrosis reaction, the fluorescence intensity reached the maximum, and the degree of TauK18 fibrosis remained basically unchanged. Specifically, according to the construction method of the early ThT fluorescence experiment in Example 1 (Table 2), when the fluorescence intensity is observed to remain almost unchanged, the detection of the microplate reader is suspended, and 5 μL of xanthohumol of different concentrations are added to each system , an equal volume of DMSO was used as a control, and continued to be placed in a microplate reader at a constant temperature of 37°C for 17 hours, ...

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Abstract

The invention discloses application of xanthohumol as an inhibitor of abnormal aggregation of Tau proteins to the preparation of a drug for preventing/treating a Tau protein disease or a functional food or health care product for preventing/alleviating the Tau protein disease. The invention discloses that xanthohumol has an effect of effectively inhibiting the abnormal aggregation function of Tauproteins, so that the pathological process of the Tau protein disease can be prevented, and meanwhile, since xanthohumol is non-toxic, xanthohumol can be used as an anti-Tau protein disease drug for the treatment of neurodegenerative diseases.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of xanthohumol in drugs for inhibiting abnormal aggregation inhibitors of tau protein and preventing / treating tau protein diseases. Background technique [0002] In recent years, the number of elderly patients with neurodegenerative diseases has been increasing year by year, manifested as cognitive impairment, memory loss, behavior and motor ability weakening and so on. One of these protein deposits is neurofibrillary tangles in nerve cells, which are formed by abnormal aggregation and fibrillation of Tau protein, leading to structural changes, functional degeneration, and even apoptosis of neurons. More and more researchers believe that Tau protein is an effective target for neurodegenerative diseases. Common neurodegenerative diseases include Alzheimer's disease, frontotemporal dementia, progressive supranuclear palsy, Pick's disease, Parkinson'...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/12A61P25/28A23L33/10A23L33/105
CPCA23L33/10A23L33/105A23V2002/00A61K31/12A61P25/28A23V2200/30A23V2250/2116
Inventor 肖时锋吴秋平张默涵
Owner SHENZHEN UNIV
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