Astragaloside IV suppresses collagen production of activated hepatic stellate cells via oxidative stress-mediated p38 MAPK pathway

• Published in: Free radical biology & medicine Vol. 60; pp. 168 - 176
• Main Authors: Li, Xiaoming, Wang, Xiaoli, Han, Cuiyan, Xing, Guihua, Zhou, Li, Li, Gang, Niu, Yingcai
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2013
• Subjects: Animals; Antioxidant; antioxidant activity; Astragaloside IV; collagen; Collagen - metabolism; extracellular matrix; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; fibrosis; Free radicals; genes; glutathione; Hepatic fibrosis; Hepatic stellate cell; Hepatic Stellate Cells - cytology; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - metabolism; Humans; Imidazoles - pharmacology; lipid peroxidation; Lipid Peroxidation - drug effects; liver; liver cirrhosis; Liver Cirrhosis - drug therapy; Liver Cirrhosis - metabolism; Liver Cirrhosis - physiopathology; MAP Kinase Signaling System - drug effects; mitogen-activated protein kinase; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; oxidative stress; Oxidative Stress - drug effects; p38 MAPK; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; Primary Cell Culture; Pyridines - pharmacology; Rats; reactive oxygen species; Reactive Oxygen Species - metabolism; Saponins - administration & dosage; signal transduction; Triterpenes - administration & dosage; Hepatic fibrosis; Free radicals; HO-1; LPO; Astragaloside IV; Antioxidant; p38 MAPK; ECM; α-SMA; AS-IV; Nrf2; FBS; ROS; HSC; TGF-β; Hepatic stellate cell; GSH; BSO
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2013.02.027

Oxidative stress is involved in hepatic fibrogenesis. Activation of hepatic stellate cells (HSCs), the key effectors in hepatic fibrogenesis, is characterized by overproduction of extracellular matrix. Astragaloside IV, the active component of Radix Astragali, has antioxidant properties and antifibrotic potential in renal fibrosis. Little is known about the role of astragaloside IV in liver and its involvement in hepatic fibrosis. This study aims at evaluating the antifibrotic potential of astragaloside IV and characterizing involved signal transduction pathways in culture-activated HSCs. Our results show that astragaloside IV attenuates oxidative stress in culture-activated HSCs, as demonstrated by scavenging reactive oxygen species and reducing lipid peroxidation, and elevates the level of cellular glutathione by stimulating Nrf2gene expression. Depletion of cellular glutathione by buthionine sulfoximine or abrogation of p38 MAPK by SB-203580 evidently eliminates the inhibitory effects of astragaloside IV on genes relevant to HSC activation. These results demonstrate that astragaloside IV inhibits HSC activation by inhibiting generation of oxidative stress and associated p38 MAPK activation and provide novel insights into the mechanisms of astragaloside IV as an antifibrogenic candidate in the prevention and treatment of liver fibrosis. [Display omitted] •Astragaloside IV attenuates oxidative stress by suppressing Nrf2 expression in vitro•Astragaloside IV inhibits HSCs activation in vitro•Both p38 MAPK and GSH mediate inhibition of HSCs activation by Astragaloside IV