Astragaloside IV suppresses collagen production of activated hepatic stellate cells via oxidative stress-mediated p38 MAPK pathway
Astragaloside IV suppresses collagen production of activated hepatic stellate cells via oxidative stress-mediated p38 MAPK pathway
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DOI：
10.1016/j.freeradbiomed.2013.02.027
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发表时间：
2013-07-01
影响因子：
7.4
通讯作者：
Niu, Yingcai
中科院分区：
文献类型：
--
作者：
Li, Xiaoming;Wang, Xiaoli;Niu, Yingcai
氧化应激参与肝纤维化的发生。肝星状细胞（hepatic stellate cells，HSC）是肝纤维化发生的关键效应细胞，其活化的特征是细胞外基质的过度产生。黄芪甲苷是黄芪的活性成分，具有抗氧化作用，对肾纤维化具有抗纤维化作用。关于黄芪甲苷在肝脏中的作用及其在肝纤维化中的作用知之甚少。本研究旨在评估黄芪甲苷的抗肝纤维化潜力，并在培养活化的HSC中表征相关的信号转导途径。我们的研究结果表明，黄芪甲苷减弱培养激活的HSC的氧化应激，表现为清除活性氧和减少脂质过氧化，并提高细胞谷胱甘肽水平，刺激Nrf 2基因的表达。通过丁硫丙磺酰亚胺消耗细胞谷胱甘肽或通过SB-203580废除p38 MAPK，明显消除了黄芪甲苷IV对HSC活化相关基因的抑制作用。这些结果表明，黄芪甲苷IV通过抑制氧化应激的产生和相关的p38 MAPK活化来抑制HSC活化，并为黄芪甲苷IV作为预防和治疗肝纤维化的抗纤维化候选物的机制提供了新的见解。(C)2013 Elsevier Inc. All rights reserved.
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. (C) 2013 Elsevier Inc. All rights reserved.