Application of oleanolic acid in preparing medicament for preventing and treating cholestasis

A technology of oleanolic acid and cholestasis, which is applied in the field of medicine and can solve problems such as cholestasis

Active Publication Date: 2014-02-26
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Recently, it has been reported that oleanolic acid can induce cholestasis in mice at doses up to 90 mg/kg or above. Which genes are expressed to c

Method used

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  • Application of oleanolic acid in preparing medicament for preventing and treating cholestasis
  • Application of oleanolic acid in preparing medicament for preventing and treating cholestasis
  • Application of oleanolic acid in preparing medicament for preventing and treating cholestasis

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Experimental program
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Embodiment 1

[0032] (1) Materials and methods

[0033] 1. Main instruments:

[0034] 5417-R low-temperature high-speed centrifuge (Eppendorf, Germany); multi-functional microplate reader (Molecular devices, USA); Mini-protein3 electrophoresis system (Bio-Rad, USA); Mini Trans-Blot transfer system (Bio-Rad, USA ); ImageQuant LAS 4000 Exposure Imager (General Electric, USA); Gradient PCR (Eppendorf, Germany); 7500 Real Time PCR System (Applied Biosystems, USA).

[0035] 2. Drugs and reagents

[0036] Oleanolic acid, lithocholic acid (purity≥98%, Shanghai Aladdin Reagent Co., Ltd.), corn oil (pharmaceutical grade, Shanghai Aladdin Reagent Co., Ltd.); Pregnenolone-16α-Carbonitrole (PCN) (purity≥98% , Sigma Company); ALT, AST, ALP, total bile acid, total bilirubin detection kit (Nanjing Jiancheng Bioengineering Institute); mouse Nrf2 interference sequence (Guangzhou Ruibo Company); Trizol reagent, RT-PCR reagent Box, qRT-PCR kit (Takara Company); Nrf2, Mrp2, Mrp3 primary antibodies (Santa Cr...

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Abstract

The invention discloses an application of oleanolic acid in preparing a medicament for preventing and treating cholestasis. A mouse with liver injury caused by over administration of lithocholic acid through experiments is used as a model, 5-20mg/kg oleanolic acid is administrated in a synergetic manner, the liver injury can be effectively alleviated and the level of bile acid can be reduced, the particular effect are that the survival rate of the mouse is remarkably increased, the activity of ALT (glutamic-pyruvic transaminase), AST (glutamic oxalacetic transaminase) and ALP (alkaline phosphatase) in serum is remarkably reduced, the necrosis degree of liver tissues is remarkably alleviated, and the content of total bile acid in liver is remarkably reduced. Liver gene and protein expression analysis prove that the oleanolic acid can remarkably up-regulate the expression of Mrp2, Mrp3 and Mrp4 and activate Nrf2, but does not have remarkable influence to other bile acid transporters and metabolic enzymes. Results indicate that the oleanolic acid can prevent and treat cholestasis liver injury induced by lithocholic acid, and the mechanism relates to a pathway of Nrf2-Mrps.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to the application of oleanolic acid in the preparation of drugs for preventing and treating cholestasis. Background technique [0002] Cholestasis is a clinical symptom of liver damage caused by excessive toxic bile acids circulating in the body or retained by the liver, which may eventually develop into fatal liver diseases, such as primary biliary cirrhosis and sclerosing cholangitis. The formation of cholestasis may be due to disturbance of bile secretion by hepatocytes or obstruction of bile ducts. Lithocholic acid (LCA) is a highly toxic hydrophobic secondary bile acid, which is produced by intestinal bacteria after dehydroxylation of the 7α position of chenodeoxycholic acid (CDCA). Significant increases in LCA levels can be detected in the blood of patients with chronic cholestatic disease, and studies have found that the accumulation of LCA in the systemic circulation o...

Claims

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Application Information

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IPC IPC(8): A61K31/56A61P1/16
Inventor 黄民毕惠嫦陈攀范晓梅姜伊鸣
Owner SUN YAT SEN UNIV
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