Application of brazilin to preparation of drug or health care product for inhibiting aggregation of beta-amyloid proteins

A technology of amyloid and brazilianin is applied in the field of application of brazilianin in the preparation of medicines or health products for inhibiting the aggregation of beta-amyloid, which can solve the problems of unclear mechanism, difficult regulation and the like, and reduce cytotoxicity. , inhibit toxicity, inhibit the effect of conformational change process

Inactive Publication Date: 2013-04-03
TIANJIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Metal chelators inhibit Aβ toxicity during Aβ aggregation by changing the concentration of metal io...

Method used

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  • Application of brazilin to preparation of drug or health care product for inhibiting aggregation of beta-amyloid proteins
  • Application of brazilin to preparation of drug or health care product for inhibiting aggregation of beta-amyloid proteins
  • Application of brazilin to preparation of drug or health care product for inhibiting aggregation of beta-amyloid proteins

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Example 1: Changes in ThT fluorescence intensity of cultures after different concentrations of brazilianin and Aβ42 co-cultured for different times

[0022] First, Aβ42 was dissolved in hexafluoroisopropanol solution to obtain a 1 mg / mL Aβ42 solution, sonicated for 10 minutes to make Aβ in a monodisperse state, freeze-dried to obtain Aβ42 dry powder, and stored at -20°C.

[0023] Weigh 5 mg of Aβ42, dissolve it in 4.03 mL of 20 mM NaOH solution, so that the final concentration of Aβ42 is 275 μM, and sonicate it for 10 minutes to fully dissolve it. Dilute with phosphate buffer saline (PBS, phosphate buffer saline) (wherein the concentration of phosphate is 100 mM, and the concentration of NaCl is 10 mM) to obtain an Aβ42 solution with a final concentration of 25 μM. Centrifuge at 16000g for 20min at 4°C, take 75% supernatant of the total volume and place it at 37°C at 200rpm for cultivation.

[0024] Dissolve 0.15 mg of brazilianin in 19.05 mL of PBS buffer to obtain a ...

Embodiment 2

[0027] Example 2: Changes in aggregate morphology of cultures after co-cultivation with different concentrations of Brazilin and Aβ42 for different periods of time

[0028] Aβ42 molecules were treated in the same manner as in Example 1, and Aβ42 solutions containing different concentrations (250, 25 and 0 μM) of brazilianin were prepared, the final concentration of Aβ42 in the solution was 25 μM, and the concentration ratio of Aβ42 to brazilianin was 1 :10 and 1:1. The above solution was incubated at 37° C. and 200 rpm.

[0029] At different incubation times, 100 μL of Aβ42 culture solution was taken, sonicated for 10 min, 5-10 μL of the solution was dropped onto a 300-mesh carbon-coated copper grid, and dried naturally. When the solution on the copper grid is almost dry, add 1% phosphotungstic acid solution (pH6.5) dropwise for 30 seconds, then absorb the excess liquid and let it dry naturally. Then observe with a transmission electron microscope (JEM100CXII), the detection...

Embodiment 3

[0031] Example 3: Changes in the secondary structure of the culture after different concentrations of brazilianin and Aβ42 co-cultured for different times

[0032]Aβ42 molecules were treated in the same manner as in Example 1, and Aβ42 culture solutions containing different concentrations of brazilianin (25, 5, 2.5, and 0 μM) were prepared, wherein the final concentration of Aβ42 was 25 μM, that is, the ratio of Aβ42 and brazilianin in the solution The concentration ratios were 1:1, 1:0.2 and 1:0.1, and the above solutions were cultured at 37°C and 200rpm. At different incubation times, 300 μL of the culture solution was added to a CD detection cell with an optical path of 1 mm for detection. The wavelength scanning range was 195-260 nm, the bandwidth was 2 nm, and the scanning speed was 100 nm / min. The experimental results were the average of three scans. Such as image 3 shown. From image 3 It can be seen that in the control group with only Aβ42, the uncultured sample af...

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Abstract

The invention discloses an application of brazilin to preparation of drug or a health care product for inhibiting aggregation of beta-amyloid proteins. Various experimental means prove that brazilin can inhibit amyloid beta 42 aggregation, can change the appearance of the amyloid beta 42 aggregation, prevents and slows down the conversion of the appearance of the amyloid beta 42 aggregation into the fibrous appearance, slows down the process of converting a secondary structure of the amyloid beta 42 into a beta-sheet structure, decreases the content of the amyloid beta 42 converted into the beta-sheet in the solution, and inhibits the amyloid beta 42 aggregation from producing a toxic effect on cells effectively. Brazilin is considered as a potential new rug or health care product molecule, can inhibit amyloid beta 42 aggregation effectively and the comformational change process of the amyloid beta 42 aggregation, reduces the cytotoxic effect generated during the amyloid beta 42 aggregation process, and is an ideal inhibitor for amyloid beta 42 aggregation.

Description

technical field [0001] The present invention relates to the use of brazilianin in the preparation of medicines and health care products for inhibiting the aggregation of beta-amyloid protein. Background technique [0002] Alzheimer's Disease (AD) is one of the most common dementias. Its symptoms are manifested as cognitive and memory dysfunction, emotional instability and other symptoms. A large number of studies have shown that in AD patients, neuronal synapse damage, neuronal apoptosis, brain atrophy, neurofibrillary tangles in brain tissue, and amyloid plaque deposition outside cerebral blood vessels and nerve cells. The main components of amyloid plaques are abnormal nerve endings, glial cells and β-amyloid protein (amyloidβ-protein, Aβ). Therefore, there is an extremely close relationship between AD and the aggregation of Aβ. [0003] Aβ is produced by the hydrolysis of transmembrane amyloid precursor protein by α, β and γ hydrolases. A[beta] generally contains 39-4...

Claims

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Application Information

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IPC IPC(8): A61K31/352A61P25/28A23L1/29A23L33/00
Inventor 董晓燕都文婕刘夫锋孙彦史清洪
Owner TIANJIN UNIV
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