Alleviation of hepatic fibrosis and autophagy via inhibition of transforming growth factor-β1/Smads pathway through shikonin

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.