Application of compound to treatment of senile dementia through antagonistic protein aggregation

A technology of senile dementia and compound, which is applied in the field of medicine to achieve the effect of improving learning and memory ability and improving effect

Inactive Publication Date: 2018-07-27
NORTHEAST NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Until March 2018, most foreign studies on epicatechin monomers focused on the exploration of the role of diabetes-related signaling pathways. There are related literature studies on the exploratio

Method used

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  • Application of compound to treatment of senile dementia through antagonistic protein aggregation
  • Application of compound to treatment of senile dementia through antagonistic protein aggregation
  • Application of compound to treatment of senile dementia through antagonistic protein aggregation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1 Thioflavin T assay (ThT) for epicatechin inhibiting Aβ42 monomer aggregation and MTT assay for inhibiting Aβ42 oligomer-mediated neurotoxic injury

[0029] The protein Aβ protein was synthesized by Nanjing Taopu Biological Co., Ltd., with a purity greater than 95%. The compound epicatechin was provided by Shanghai Yuanye Biological Company. The Aβ monomer powder is stored at -80°C. When it is taken out for the first time, it should be allowed to stand at room temperature for 30 minutes, then diluted with hexafluoroisopropanol (HFIP) to 1.0 mg / ml, left to stand for at least 2 hours, and ultrasonicated for 30 minutes to destroy the existing polysaccharides. Polymer structure, after drying at low temperature, store at -20°C immediately. Thioflavin T (Thioflavin T) was purchased from Sigma (product number T3516-5g). Weigh 0.032g of ThT powder and dissolve it in 20ml of 20mM Tris-HCl (pH 7.4) solution to obtain 5mM ThT mother solution, which is diluted to 5uM whe...

Embodiment 2

[0034] Example 2 Epicatechin and Aβ Protein Transmission Electron Microscopy Experiment (Transmission electron microscopy, TEM)

[0035] The pretreatment was as in Example 1, and then, 5ul of the Aβ protein sample incubated at 37°C for 24 hours was dropped on the surface of a 300-mesh carbon-coated copper grid, air-dried, and negatively stained with 2% (w / v) sodium phosphotungstic acid After 30 seconds, let stand at room temperature for about 4 hours, use JEM-100CXII transmission electron microscope system (JEOL inc., Tokyo, Japan) to detect and take pictures, and the accelerating voltage is 80kV.

[0036] The observation results are attached figure 2 . Compared with the untreated control group, the fiber density, length and width of the Aβ protein in the experimental group (EPI) added with epicatechin compounds decreased significantly in a concentration-dependent manner, while the other group of cholinesterase inhibitors Aricept (donepezil hydrochloride) has no effect on t...

Embodiment 3

[0037] Example 3 Epicatechin and Aβ protein circular dichroism experiment (CD)

[0038] Aβ monomer was mixed with drugs, the final concentration of Aβ was 20uM, and the final concentrations of drugs were 0uM, 10uM, 20uM and 40uM respectively, and after incubation at 37°C for 12 hours with slow shaking, the J-810 spectrometer (Jasco, Japan) was used to detect. The wavelength range is 190-250nm, the resolution is 0.5nm, the spectral width is 2nm, the scanning speed is 100nm / min, the response time is 1s, and the measurement temperature is normal temperature. The solution was added to a quartz cuvette with an optical path of 0.1 mm for measurement, and each experiment was repeated three times. Subtract the buffer curve from the scan curve obtained each time as the experimental result, each experiment was repeated three times, and the average value was given.

[0039] Using the software Jascow32 data analysis provided by the instrument manufacturer to find (attached image 3 ), t...

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Abstract

The invention discloses application of epicatechin to antagonistic beta amyloid protein aggregation, cognition and memory ability improvement and age pigment reduction. AD (Alzheimer's disease) belongs to a neurodegenerative disease using nerve cell fiber entanglement, beta amyloid protein (A beta) plaque deposition and cognitive function reduction as pathological features, wherein the A beta protein extracellular toxicity accumulation is regarded as one of the major link of the occurrence of the AD. The effect that the epicatechin can obviously inhibit the fiber formation through the beta amyloid protein aggregation, inhibit the formation of a beta secondary structure, improve the space memory study capability of AD mice, and obviously clear the amyloid plaque in the APP/PS1 dual transgenic AD model mouse brain tissue is discovered. The result shows that the epicatechin can be applied to the treatment of AD and relevant medicine research and development.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to the application of epicatechin in the preparation of medicines for treating Alzheimer's disease by antagonizing the accumulation of beta amyloid 1-42 (Aβ42) as a target. Background technique [0002] Alzheimer's disease (AD), also known as Alzheimer's disease, is clinically manifested as psychomotor abnormalities, language disorders, cognitive and memory impairments, and is a common progressive neurological decline in the elderly. According to the World Alzheimer's Report 2009, the number of people living with the disease will soar to 150 million by 2050 [1] . [0003] The most widely accepted theory about the pathogenesis of AD is the Aβ theory marked by the oligomerization of β-amyloid protein and the formation of fibrous precipitates. [2] . Under normal physiological conditions, the generation and degradation of Aβ from the hydrolysis of β-amyloid precursor pr...

Claims

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Application Information

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IPC IPC(8): A61K31/353A61P25/28
CPCA61K31/353
Inventor 李晓萌王立春刘孜育袁瑞魏溦李江
Owner NORTHEAST NORMAL UNIVERSITY
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