Tong Liu1, Ling Xu2, Chengfen Wang1, Kan Chen1, Yujing Xia1, Jingjing Li1, Sainan Li1, Liwei Wu1, Jiao Feng1, Shizan Xu1,3, Wenwen Wang1, Xiya Lu1, Xiaoming Fan4, Wenhui Mo5, Yingqun Zhou1, Yan Zhao1, Chuanyong Guo1. 1. Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. 2. Department of Gastroenterology, Shanghai Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. 3. Shanghai Tenth Hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai, China. 4. Department of Gastroenterology, Jinshan Hospital of Fudan University, Shanghai, China. 5. Department of Gastroenterology, Minhang Hospital, Fudan University, Shanghai, China.
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 CCl4 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.
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 CCl4 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.
Authors: Hang Yu Wang; Can Li; Wei Hua Liu; Feng Mei Deng; Yan Ma; Li Na Guo; De Hua Kong; Kang An Hu; Qin Liu; Jiang Wu; Jing Sun; Yi Lun Liu Journal: J Cell Physiol Date: 2019-09-11 Impact factor: 6.384