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Alleviation of hepatic fibrosis and autophagy via inhibition of transforming growth factor‐ β 1/Smads pathway through shikonin
Author(s) -
Liu Tong,
Xu Ling,
Wang Chengfen,
Chen Kan,
Xia Yujing,
Li Jingjing,
Li Sainan,
Wu Liwei,
Feng Jiao,
Xu Shizan,
Wang Wenwen,
Lu Xiya,
Fan Xiaoming,
Mo Wenhui,
Zhou Yingqun,
Zhao Yan,
Guo Chuanyong
Publication year - 2019
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.14299
Subject(s) - hepatic stellate cell , medicine , transforming growth factor , hepatic fibrosis , autophagy , cirrhosis , fibrosis , extracellular matrix , liver injury , tissue inhibitor of metalloproteinase , intraperitoneal injection , cancer research , pathology , matrix metalloproteinase , chemistry , biochemistry , apoptosis
Abstract Background and Aim Liver fibrosis is a worldwide clinical challenge during the progression of chronic liver disease to liver cirrhosis. Shikonin is extracted from the root of Lithospermum erythrorhizon with antioxidant, anti‐inflammatory, anticancer, and wound‐healing properties. The study aims to investigate the protective effect of shikonin on liver fibrosis and its underlying mechanism. Methods Two liver fibrosis models were established in male C57 mice by intraperitoneal injection of CCl 4 or bile duct ligation. Shikonin was administered orally three times weekly at a dose of 2.5 or 5 mg/kg. Protein and mRNA expressions were assayed by quantitative real‐time polymerase chain reaction, Western blotting, and immunohistochemical staining. Results Shikonin significantly inhibited activation of hepatic stellate cells and extracellular matrix formation by downregulating the transforming growth factor‐β1 expression and maintaining the normal balance between metalloproteinase‐2 and tissue inhibitor of metalloproteinase‐1. Shikonin also decreased hepatic stellate cell energy production by inhibiting autophagy. Conclusions The results confirmed that shikonin attenuated liver fibrosis by downregulating the transforming growth factor‐β1/Smads pathway and inhibiting autophagy.