title: Astragaloside IV suppresses collagen production of activated hepatic stellate cells via oxidative stress-mediated p38 MAPK pathway.
abstract: 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.
authors: Institute of Medicine, Qiqihar Medical University, Qiqihar 161006, China.
authors: Xiaoming
authors: X
authors: Li
authors: Xiaoli
authors: X
authors: Wang
authors: Cuiyan
authors: C
authors: Han
authors: Xiaoli
authors: X
authors: Wang
authors: Guihua
authors: G
authors: Xing
authors: Li
authors: L
authors: Zhou
authors: Gang
authors: G
authors: Li
authors: Yingcai
authors: Y
authors: Niu
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D061251:Primary Cell Culture; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins / Q000008:administration & dosage*; D014315:Triterpenes / Q000008:administration & dosage*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D011725:Pyridines; D017382:Reactive Oxygen Species; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D003094:Collagen; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580