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GPR35 receptor stimulant in salviae miltiorrhizae, inhibitor of Ca2+-ATPase and application

A receptor agonist, Salvia miltiorrhiza technology, applied in non-central analgesics, medical preparations containing active ingredients, anti-inflammatory agents, etc. Effect

Inactive Publication Date: 2016-04-27
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, there is no report on the dual-target effects of phenolic acids in Salvia miltiorrhiza on GPR35 receptors and salvianolic acid A and salvianolic acid C.

Method used

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  • GPR35 receptor stimulant in salviae miltiorrhizae, inhibitor of Ca2+-ATPase and application
  • GPR35 receptor stimulant in salviae miltiorrhizae, inhibitor of Ca2+-ATPase and application
  • GPR35 receptor stimulant in salviae miltiorrhizae, inhibitor of Ca2+-ATPase and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Example 1: Preliminary pharmacological characterization of phenolic acids in Danshen on HT-29 cells and A431 cells

[0017] Materials Salvianolic acid D was obtained from Zhu Jingguo Laboratory of Dalian University of Technology, and other compounds were purchased from Shanghai Yuanye Biotechnology Co., Ltd.; HT-29 cells and A431 cells were purchased from the Shanghai Cell Bank of the Chinese Academy of Sciences; , bradykinin, thapsigargin and cyclopiazonic acid were purchased from Sigma. The detection platform is the third generation of Corning Imager, the detected signal is the wavelength shift caused by cell dynamic mass reset (DMR).

[0018] HT-29 cells and A431 cells in the logarithmic growth phase were inoculated in different wells of a 384-well cell plate, the inoculation volume of each well was 40 μL, and the number of cells inoculated in each well was 3.2×10 4 and 2.5×10 4 First, place the inoculated cell plate in a cell incubator and culture it for 20-22 h...

Embodiment 2

[0021] Example 2: Discovery and verification of certain phenolic compounds in Salvia miltiorrhiza acting on GPR35 receptors

[0022] by comparison figure 1 A and 1B, it is deduced that the targets of salvianolic acid A, salvianolic acid B, salvianolic acid C, shikonin and danshensu are GPR35 receptors, and this experiment is verified and analyzed from three angles of stimulation, desensitization and antagonism .

[0023]The first is the stimulation analysis. Salvianolic acid A, salvianolic acid B, salvianolic acid C, shikonin and danshensu were applied to HT-29 cells. The concentration gradient of each compound was 250 μM, 125 μM, 62.5 μM, 31.25 μM , 15.625μM, 7.813μM, 3.9063μM, 1.953μM, 0.977μM, 0.488μM, 0.244μM, 0.122μM, 0.0610μM, the results are as follows image 3 As shown, the dose-response curves of salvianolic acid A, salvianolic acid C and shikonic acid were single-phase "S" type, and all reached saturation response, the corresponding EC 50 The values ​​are 37.69±3....

Embodiment 3

[0028] Example 3: Dual-target action mechanism of salvianolic acid A and salvianolic acid C

[0029] Combined with the preliminary characterization of salvianolic acid A and salvianolic acid C on HT-29 cells and A431 cells, DMR signals of acetylcholine, bradykinin and histamine all existed after pretreatment of cells with salvianolic acid A and salvianolic acid C Certain changes, because acetylcholine receptors, bradykinin receptors and histamine receptors are all Gαq-coupled receptors, indicating that the activation pathways of salvianolic acid A and salvianolic acid C may be related to Gαq. Because the calcium flow is generated when the Gαq pathway is activated, and the calcium flow is also generated when the calcium pump is activated, so the Gαq pathway and the calcium pump have heterologous desensitization, so it is inferred that salvianolic acid A and salvianolic acid C may act on Ca 2+ -ATPase. In order to verify that salvianolic acid A and salvianolic acid C act on Ca ...

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Abstract

The invention relates to the discovering of the action targets of traditional Chinese medicine salviae miltiorrhizae and widening of clinical application range, in particular to discovering of the new action targets of phenolic acid compounds in the salviae miltiorrhizae and new clinical application of the phenolic acid compounds. The phenolic acid compounds include similar-structured compounds such as protocatechuic aldehyde, tanshinol, caffeic acid, alkannic acid, salvianolic acid A, salvianolic acid B, salvianolic acid C and salvianolic acid D, the derivatives of the similar-structured compounds and the pharmaceutically-acceptable salt-forming compounds of the similar-structured compounds. In vitro cell experiments show that the compounds act on the orphan receptor GPR35 and current researches show that the orphan receptor GPR35 is related to diseases such as cardiac failure, hypertension, coronary heart disease, metabolic syndrome, asthma, pain, inflammation and cancer, so that the clinical application range of the compounds can be widened. In addition, the fact that the compounds have a double-target effect is discovered, and certain guidance is provided for the new clinical application.

Description

technical field [0001] The present invention relates to the discovery of the action target of the traditional Chinese medicine Salvia miltiorrhiza and broadening the scope of clinical application, specifically the discovery of the new action target of the phenolic acid compounds in the salvia miltiorrhiza and the new clinical application of such compounds. Including protocatechualdehyde, danshensu, caffeic acid, shikonic acid, salvianolic acid A, salvianolic acid B, salvianolic acid C, salvianolic acid D and other structural compounds and their derivatives, and their pharmaceutically acceptable Salt-forming compound; the target is GPR35 and Ca 2+ -ATPase; the new clinical application is the prevention and treatment of diseases such as heart failure, hypertension, coronary heart disease, metabolic syndrome, asthma, pain, inflammation and cancer. Background technique [0002] Salvia miltiorrhiza is the dry root and rhizome of Salvia miltiorrhiza Bge, which was first recorded ...

Claims

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Application Information

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IPC IPC(8): A61K36/537A61P3/00A61P11/06A61P29/00A61P35/00A61P9/00A61P25/06A61P9/14A61P9/04A61P9/12
Inventor 梁鑫淼王纪霞张秀莉魏来史丽颖侯滔
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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