Withaferin A Exerts Preventive Effect on Liver Fibrosis through Oxidative Stress Inhibition in a Sirtuin 3-Dependent Manner.
Withaferin A Exerts Preventive Effect on Liver Fibrosis through Oxidative Stress Inhibition in a Sirtuin 3-Dependent Manner.
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DOI：
10.1155/2020/2452848
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发表时间：
2020
影响因子：
--
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Gu J;Chen C;Wang J;Chen T;Yao W;Yan T;Liu Z
Sirtuin 3（SIRT 3）是一种脱乙酰酶，参与许多炎症相关疾病的发展，包括肝纤维化。睡茄素A（Withaferin A，WFA）是一种来源于睡茄植物的生物活性成分，具有广泛的药理活性，但SIRT 3在WFA诱导的抗纤维化作用中的调控作用却知之甚少。本研究旨在探讨SIRT 3在WFA诱导的肝纤维化抗氧化作用中的作用。我们的研究证实，WFA减弱血小板衍生生长因子BB-（PDGF-BB-）诱导的肝纤维化，并促进PDGF-BB诱导的SIRT 3活性和表达在JS 1细胞中。SIRT 3沉默减弱了WFA在活化的JS 1细胞中的抗纤维化和抗氧化作用。此外，WFA抑制四氯化碳（CCl 4-）诱导的肝损伤，胶原沉积和纤维化;增加SIRT 3的表达;并抑制CCl 4诱导的C57/BL 6小鼠纤维化肝脏的氧化应激。此外，WFA的抗纤维化和抗氧化作用在CCl 4诱导的WT（129 S1/SvImJ）小鼠中可用，但在CCl 4诱导的SIRT 3敲除（KO）小鼠中不可用。我们的研究表明，WFA抑制肝纤维化通过抑制氧化应激的SIRT 3依赖的方式。WFA可能是一种潜在的抗肝纤维化药物。
Sirtuin 3 (SIRT3) is a deacetylase involved in the development of many inflammation-related diseases including liver fibrosis. Withaferin A (WFA) is a bioactive constituent derived from the Withania somnifera plant, which has extensive pharmacological activities; however, little is known about the regulatory role of SIRT3 in the WFA-induced antifibrogenic effect. The current study is aimed at investigating the role of SIRT3 in WFA-induced antioxidant effects in liver fibrosis. Our study verified that WFA attenuated platelet-derived growth factor BB- (PDGF-BB-) induced liver fibrosis and promoted PDGF-BB-induced SIRT3 activity and expression in JS1 cells. SIRT3 silencing attenuated the antifibrogenic and antioxidant effects of WFA in activated JS1 cells. Moreover, WFA inhibited carbon tetrachloride- (CCl4-) induced liver injury, collagen deposition, and fibrosis; increased the SIRT3 expression; and suppressed the CCl4-induced oxidative stress in fibrotic livers of C57/BL6 mice. Furthermore, the antifibrogenic and antioxidant effects of WFA could be available in CCl4-induced WT (129S1/SvImJ) mice but were unavailable in CCl4-induced SIRT3 knockout (KO) mice. Our study suggested that WFA inhibited liver fibrosis through the inhibition of oxidative stress in a SIRT3-dependent manner. WFA could be a potential compound for the treatment of liver fibrosis.
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