Premium
Protective effect of isochlorogenic acid B on liver fibrosis in non‐alcoholic steatohepatitis of mice
Author(s) -
Liu Xin,
Huang Kai,
Niu Ziran,
Mei Dan,
Zhang Bo
Publication year - 2019
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.13122
Subject(s) - steatohepatitis , hepatic stellate cell , fibrosis , endocrinology , medicine , hydroxyproline , oxidative stress , fatty liver , chemistry , disease
Liver fibrosis is a common symptom of non‐alcoholic steatohepatitis ( NASH ) and a worldwide clinical issue. The miR‐122/ HIF ‐1α signalling pathway is believed to play an important role in the genesis of progressive fibrosis. Isochlorogenic acid B ( ICAB ), naturally isolated from Laggera alata , is verified to have antioxidative and hepatoprotective properties. The aim of this study was to investigate the effect of ICAB on liver fibrosis in NASH and its potential protective mechanisms. NASH was induced in a mouse model with a methionine‐ and choline‐deficient ( MCD ) diet for 4 weeks, and ICAB was orally administered every day at three doses (5, 10 and 20 mg/kg). Pathological results indicated that ICAB significantly improved the pathological lesions of liver fibrosis. The levels of serum alanine aminotransferase ( ALT ), aspartate aminotransferase ( AST ) and hepatic hydroxyproline (Hyp), cholesterol ( CHO ) and triglyceride ( TG ) were also significantly decreased by ICAB . In addition, ICAB inhibited hepatic stellate cells ( HSC s) activation and the expressions of hepatic genes involved in liver fibrosis including LOX , TGF ‐β1, MCP ‐1, COL 1α1 and TIMP ‐1. ICAB also attenuated liver oxidative stress through Nrf2 signalling pathway. What is more, the decreased levels of miR‐122 and over‐expression of hepatic HIF ‐1α could be reversed by ICAB treatment. These results simultaneously confirmed that ICAB had a significant protective effect on fibrosis in NASH by inhibiting oxidative stress via Nrf2 and suppressing multiple profibrogenic factors through miR‐122/ HIF ‐1α signalling pathway.