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Application of kinsenoside to preparation of medicines for eliminating brain amyloid beta protein clots

A technology of amyloid and aureus glycosides is applied in the directions of drug combination, pharmaceutical formulation, medical preparation containing active ingredients, etc., which can solve the problem of difficulty in taking both Aβ plaque clearance and inhibition of neuroinflammation, strong neuroinflammation response, and effective It can achieve good clinical application prospects, inhibit neuroinflammation, and improve learning and cognitive functions.

Active Publication Date: 2019-12-20
福建金兰厚普生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these drugs are difficult to take into account the clearance of Aβ plaques and the inhibition of neuroinflammation, the neuroinflammation response is strong, and the effect is not good
[0006] Clematis glucoside is a chemical component extracted from Clematis clematis of Orchidaceae. Pharmacological studies have shown that it has the effects of lowering blood sugar, lowering blood fat, protecting liver and improving osteoporosis, etc., but no other effects have been found. Reports of any effect on amyloid beta

Method used

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  • Application of kinsenoside to preparation of medicines for eliminating brain amyloid beta protein clots
  • Application of kinsenoside to preparation of medicines for eliminating brain amyloid beta protein clots
  • Application of kinsenoside to preparation of medicines for eliminating brain amyloid beta protein clots

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Experiment of improving mitochondrial energy metabolism of microglial cells with auroside

[0036] An important hallmark of microglial aging is decreased cellular aerobic respiration, resulting in decreased ATP production and decreased phagocytic clearance.

[0037] The basal oxygen consumption capacity (OCR) of cells treated with auroside was detected by Seahorse XF Mito Stress Test Kit (Agilent Technologies). The specific steps are as follows: ① first inoculate BV2 microglial cells into XF 96-well cell culture plate (5000 cells / well), and divide them into two groups on average, with 6 wells in each group; ② add solvent control DMSO to the cells in the two groups at 12 hours and anointing solution (final concentration: 20 μM), respectively as the control group and auroglucoside group, each treated 6 replicate wells, and continued to culture for 24 hours; ③ Discard the medium, wash it twice with PBS, and then add In XF medium, XFe 96 ExtracellularFlux analyz...

Embodiment 2

[0043] Example 2 Experiment of auroside inhibiting inflammation of microglial cells

[0044] Lipopolysaccharide (LPS) was used to stimulate microglia to induce M1-type inflammatory response as a model of microglial inflammation.

[0045] BV2 microglial cells were seeded in a 12-well cell culture plate, 100,000 cells / well, and after 12 hours, they were pretreated with auroside with a final concentration of 20 μM (the molar concentration of the stock solution was 80 mM) for 1 hour. The cells pretreated with auroglutinin were used as the control group, and then treated with LPS (final concentration 1 μg / ml) for 12 hours and 24 hours, respectively, and then the cells were lysed with Trizol reagent to extract RNA. After the RNA was extracted, 1 μg of total RNA was taken from each sample and reverse-transcribed with random primers using reverse transcriptase to obtain cDNA. The expression of the internal reference gene β-actin and M1-type inflammatory factors IL-6, TNF-α and iNOS...

Embodiment 3

[0056] Example 3-Auroglutin enhances microglia phagocytosis of amyloid protein experiment

[0057] The phagocytosis of oligomerized amyloid Aβ1-42 (AD marker) by primary microglia was used as a model.

[0058] The primary microglial cells were inoculated in a 24-well plate with cell slides, and after 12 hours, they were pretreated with auroside with a final concentration of 20 μM (the molar concentration of the stock solution was 80 mM) for 1 hour, and another unused gold wire was taken The cells pretreated with lotus root were used as the control group, and then FITC-labeled amyloid Aβ1-42 oligomers were added. After reacting for 6 hours, the cells were washed with pre-cooled PBS buffer for 3 times to remove unphagocytosed amyloid, and then treated with Cells were fixed with 4% formaldehyde solution, and then microglia were labeled by immunofluorescent staining.

[0059] Immunofluorescence staining steps are: ① 500 μl 0.5% Triton X-100 incubated at room temperature for 20 ...

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Abstract

The invention discloses an application of kinsenoside or pharmaceutically acceptable salts thereof to preparation of medicines for eliminating brain amyloid beta protein clots. The kinsenoside or pharmaceutically acceptable salts thereof can effectively eliminate the brain amyloid beta protein clots, and besides, can restrain neurogenic inflammation.

Description

technical field [0001] The present invention relates to a new pharmaceutical application of the compound, in particular to the application of auroside or a pharmaceutically acceptable salt thereof in the preparation of a drug for removing brain beta amyloid plaques. Background technique [0002] Alzheimer's disease (AD), commonly known as senile dementia, is a progressive neurodegenerative disease. The main clinical symptoms are cognitive decline, short-term memory decline, and gradual loss of self-care ability. According to demographic forecasts, by 2050, the number of Alzheimer's disease patients worldwide will exceed 100 million, and the global economic burden is expected to reach 9 trillion US dollars. However, due to the complexity of Alzheimer's disease, its pathogenesis is still unclear, and there is no clinically effective treatment. Therefore, the development of effective drugs for the prevention and treatment of Alzheimer's disease is still an urgent problem to be...

Claims

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Application Information

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IPC IPC(8): A61K31/7048A61P25/28
CPCA61K31/7048A61P25/28
Inventor 袁增强潘瑞远廖亚金张海燕
Owner 福建金兰厚普生物科技有限公司
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