肝星状细胞
木犀草素
蛋白激酶B
SMAD公司
PI3K/AKT/mTOR通路
癌症研究
肝纤维化
纤维化
化学
体内
转化生长因子
细胞生物学
信号转导
生物
药理学
医学
内科学
内分泌学
生物化学
抗氧化剂
槲皮素
生物技术
作者
Jie Li,Xingxia Li,Wei‐Heng Xu,Shaozhan Wang,Zhenlin Hu,ZhongXiang Zhang,Xing Deng,Jing Wang,Junping Zhang,Cheng Guo
摘要
Abstract Background & Aims Luteolin has been reported to exert antifibrogenic effects in CC l 4 ‐induced hepatic fibrosis in mice. However, limited information is available on the cellular and molecular events responsible for this effect. This study focused on the action of luteolin on hepatic stellate cells ( HSC s) and the relevant signalling molecules and pathways as well as the antifibrotic efficacy in multiple models of fibrosis. Methods The in vitro effect of luteolin on rat HSC s and HSC ‐T6 cells was assessed using proliferation assays, invasion chamber, quantitative real‐time PCR analysis and Western blotting. The in vivo effect of luteolin on progression of fibrosis was assessed in three experimental rat models induced by CC l 4 , dimethylnitrosamine ( DMN ) and bile duct ligation ( BDL ). Results Luteolin inhibited proliferation, migration, collagen synthesis as well as expression of fibrosis‐related genes in the activated HSC s and HSC ‐T6 cells stimulated with or without transforming growth factor‐β1( TGF β1) or platelet‐derived growth factor ( PDGF ). Luteolin induced HSC apoptosis associated with the increased caspase 3 activity and p53 expression, and induced G1 arrest with the decreased expression of bcl‐2, Cyclin E and p‐Cdk‐2. Moreover, luteolin significantly inhibited PDGF and TGF β1‐simulated phosphorylation of AKT and Smad pathway. In vivo study showed that luteolin administration markedly alleviated hepatic fibrosis along with reduced elevations of alanine aminotransferase and aspartate aminotransferase. HSC s were found to undergo apoptosis and decreased expression of p‐Smad2 and p‐ AKT in luteolin‐treated animals. Conclusions This study demonstrates that luteolin prevents the progression of liver fibrosis through multiple mechanisms and indicates that luteolin has potential for effective treatment of liver fibrosis.
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