Application of compound to treatment of senile dementia through protein accumulation reduction

A technology for senile dementia and compound, applied in the field of medicine, can solve problems such as no reports, and achieve the effects of improving learning and memory ability, improving learning and memory function, and inhibiting the formation of Aβ amyloid deposition.

Inactive Publication Date: 2018-11-06
NORTHEAST NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Hyperoside is widely distributed and has various physiological activities such as anti-inflammatory, antispasmodic, diuretic, cough-relieving, blood pressure-lowering, cholesterol-lowering, protein assimilation, local and central analgesia, and protection of heart and cerebrovascular. An important natural product, but there is no report on the application of antagonizing Aβ protein accumulation to treat AD

Method used

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  • Application of compound to treatment of senile dementia through protein accumulation reduction
  • Application of compound to treatment of senile dementia through protein accumulation reduction
  • Application of compound to treatment of senile dementia through protein accumulation reduction

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1 Thioflavin T assay (ThT) for hyperoside inhibiting the aggregation of Aβ42 monomers and MTT assay for inhibiting neurotoxic damage mediated by Aβ42 oligomers

[0029] The protein Aβ protein was synthesized by Nanjing Taopu Biological Co., Ltd., with a purity greater than 95%. The compound hyperin and its isomer isoquercetin (Isoquercetin) were 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 excess Polymer structure, after drying at low temperature, store at -20°C immediately. Thioflavin T (ThioflavinT) was purchased from Sigma (product number T3516-5g). Weigh 0.032g of ThT powder and dissolve it in 20ml of 20mM Tris-HCl (pH7.4) solution to obtain 5mM ThT mothe...

Embodiment 2

[0034] Example 2 Hyperin and Aβ Protein Transmission Electron Microscopy Experiment (Transmissionelectronmicroscopy, 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 (JEO Linc., Tokyo, Japan) to detect and take pictures, and the accelerating voltage is 80kV.

[0036] The observation results are attached figure 2 . Compared with the control group without drug addition, the experimental group (HPY) Aβ protein fiber density, length and width decreased significantly in a concentration-dependent manner with the addition of hyperoside compounds, while the other group of cholinesterase inhibitors Aricept (donepezil hydrochloride) has no effect on ...

Embodiment 3

[0037] Example 3 Hyperin 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 ), the A...

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PUM

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Abstract

The invention discloses application of hyperoside to antagonism of beta amyloid protein accumulation, improvement on cognition and memory and reduction in senile plaques. Alzheimer's disease (AD) is aneurodegenerative disease characterized by neurofibrillary tangles, beta amyloid protein (Abeta) plaque deposition and cognitive decline, and extracellular toxic accumulation of Abeta protein is considered to be one of main links in pathogenesis of the AD. The invention finds that the hyperoside and an isomer thereof, namely isoquercetin, can significantly inhibit fiber formation caused by accumulation of beta amyloid protein 1-42 monomers, inhibit formation of a beta secondary structure, improve the spatial memory learning ability of an AD mouse and significantly eliminate amyloid plaques ina brain tissue of an APP / PS1 double-transgenic AD model mouse, which indicates that the hyperoside can be applied to treatment of the Alzheimer's disease and research and development of related medicines.

Description

technical field [0001] The invention belongs to the technical field of medicines, and specifically relates to the application of hyperoside in the preparation of medicines for treating Alzheimer's disease by antagonizing the accumulation of β-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 impairment, 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 prote...

Claims

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Application Information

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IPC IPC(8): A61K31/7048A61P25/28
CPCA61K31/7048A61P25/28
Inventor 李晓萌王立春姜波迟爽魏溦李江
Owner NORTHEAST NORMAL UNIVERSITY
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