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Application of compound in treatment of senile dementia by inhibiting amyloid protein accumulation

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

Inactive Publication Date: 2018-07-24
NORTHEAST NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Until March 2018, there were about 165 foreign literature searches for research reports on emodin monomers in Alzheimer's disease, most of which focused on the exploration of emodin's role in Alzheimer's disease-related signaling pathways. However, there is no report on the application of antagonizing the accumulation of Aβ protein in the treatment of AD.

Method used

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  • Application of compound in treatment of senile dementia by inhibiting amyloid protein accumulation
  • Application of compound in treatment of senile dementia by inhibiting amyloid protein accumulation
  • Application of compound in treatment of senile dementia by inhibiting amyloid protein accumulation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1 Thioflavin T assay (ThT) of emodin inhibiting Aβ42 monomer aggregation and MTT assay of 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 emodin 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 excess 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 when used.

[0030]When ...

Embodiment 2

[0034] Example 2 Emodin 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 (EMO) added with emodin compounds decreased significantly in a concentration-dependent manner, while the other group of cholinesterase inhibitors, Aricept (Donepezil hydrochloride) had no effect on the inhibi...

Embodiment 3

[0037] Embodiment 3 Emodin 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...

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Abstract

The invention discloses application of emodin in antagonizing accumulation of amyloid beta protein, improving cognitive memory ability and reducing senile plaques. Alzheimer's disease (AD) is neurodegenerative disease characterized by neurofibrillary tangles, amyloid beta (A beta) protein plaque deposition and cognitive decline, wherein A beta protein extracellular toxicity accumulation is considered to be one of the main links in the pathogenesis of AD. The emodin is found to be capable of significantly inhibiting the accumulation of A beta protein 1-42 monomers so as to prevent the monomersfrom forming fibers, and is also found to be capable of inhibiting the formation of a beta secondary structure, improving the spatial memory learning ability of AD mice and obviously clearing amyloidplaques in brain tissues of APP / PS1 double-transgenic AD model mice; therefore, the emodin can be applied to the treatment of AD and the research and development of related drugs.

Description

technical field [0001] The invention belongs to the technical field of medicines, and in particular relates to the application of emodin 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 protein...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/122A61P25/28
CPCA61K31/122A61P25/28
Inventor 李晓萌王立春汪小莞李佳乐兰传健李江
Owner NORTHEAST NORMAL UNIVERSITY
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