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Use of salvianolic acid B

A technology of use and mother nucleus, applied in the field of Salvia miltiorrhiza extract

Active Publication Date: 2009-08-05
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, no studies have shown that salvianolic acid B is a novel MMP-9 inhibitor, so there is an urgent need in the field to understand these and further mechanisms by which salvianolic acid B affects cardiac function

Method used

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  • Use of salvianolic acid B

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088] Computer simulation of salvianolic acid B having a docking site with MMP-9

[0089] First, the molecular model of phenolic acid B was established using hyperchem 7.5, and a preliminary optimization was carried out. Afterwards, using guassian 03 C (quantification software), the mixed functional B3LYP method was used to select the 6-31G(d) basis group, and the precise structure optimization of the salvianolic acid B molecule was carried out. Then, the molecular docking software molsoftICM pro 3.5 was used to dock the crystal structure of salvianolic acid B and MMP-9 (code: 1GKC, only one protein chain in the crystal structure was kept, and the others were deleted).

[0090] see results figure 1 . A is the chemical structural formula of salvianolic acid B. B is the three-dimensional structural formula of salvianolic acid B. C is the docking diagram of salvianolic acid B and MMP-9. D is the spatial binding site map of salvianolic acid B and MMP-9.

[0091] The above r...

Embodiment 2

[0093] Gelatin zymography detection of salvianolic acid B directly inhibits MMP-9 activity (in vitro)

[0094] Acute myocardial infarction can cause a rapid upregulation of MMP-9 enzyme activity, followed by an upregulation of MMP-2 activity. Therefore, in this study, the ischemic tissue of rats with acute myocardial infarction was used as the protease source of MMP-9 and MMP-2.

[0095] The tissue in the ischemic region of the rat heart was homogenized in cold PBS solution, centrifuged at 3000g for 10 minutes at 4°C, and the protein in the supernatant was quantified by the Lowry method.

[0096] 20 μg of protein were electrophoresed on 10% SDS-PAGE with 1% gelatin.

[0097] Wash with 2% Triton X-100 for 1 hour, and incubate at 37°C for 24 hours. The incubation solution contains 100M, 200M, and 400M salvianolic acid B buffer (50mM Tris-HCl, 5mM CaCl .5), the incubation solution without salvianolic acid was used as a control.

[0098] Finally, 0.1% Coomassie brilliant blue s...

Embodiment 3

[0102] 220-250g Wi star rats were purchased from the Shanghai Experimental Animal Center of the Chinese Academy of Sciences, and the animal model of acute myocardial infarction was prepared by ligating the left descending coronary artery of the rats.

[0103] The experiment was divided into four groups: model group (AMI), sham operation group (Sham), sham operation salvianolic acid group (SA-sham), model salvianolic acid group (SA-AMI).

[0104] Salvianolic acid was administered by gavage, 60 mg / kg each time, three days before model preparation, once a day. 24 hours after the model was prepared, the infarct tissue (myocardial tissue from the corresponding part was taken from the sham operation group) was homogenized, centrifuged at 3000 g for 10 min at 4°C, and the supernatant was taken. Protein quantification by Lowry method.

[0105] 20 g of myocardial tissue protein from rats in each group were electrophoresed on SDS-PAGE containing 1% gelatin. Wash with 2% Triton X-100 f...

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Abstract

The invention discloses application of a compound which is shown in a formula I and has a mother nucleus structure in preparing an MMP-9 enzymatic activity inhibitor. The invention also discloses a method for screening substances having the function of inhibiting the MMP-9 enzymatic activity.

Description

technical field [0001] The present invention relates to the use of the salvia miltiorrhiza extract, in particular to the use of salvianolic acid B. Background technique [0002] Salvianolic acid B (Salvianolic acid B, Sal B) is a compound with the core structure shown in formula I, also known as salvianolic acid B, which can be extracted from the dry root of the labiatae plant Salvia (Salviamiltiorrhiza Bunge) , is a brown-yellow dry powder; taste slightly bitter, astringent; soluble in water, ethanol, methanol: [0003] [0004] Matrix metalloproteinase (MMP) is a class of Zn-containing 2+ and Ca 2+ Proteolytic enzymes are mainly involved in the metabolism of extracellular matrix. They play important roles in angiogenesis, wound healing, tumor invasion, and fibrosis, and thus have attracted much attention. [0005] At present, more than 14 kinds of matrix metalloproteinases have been discovered, which are mainly divided into five categories: interstitial collagenases...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/343A61P9/04A61P9/00
Inventor 果德安姜宝红
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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