Withaferin A Exerts Preventive Effect on Liver Fibrosis through Oxidative Stress Inhibition in a Sirtuin 3-Dependent Manner

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 r...

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Main Authors: Jingya Gu, Chang Chen, Jue Wang, Tingting Chen, Wenjuan Yao, Tingdong Yan, Zhaoguo Liu
Format: Article
Language:English
Published: Hindawi Limited 2020-01-01
Series:Oxidative Medicine and Cellular Longevity
Online Access:http://dx.doi.org/10.1155/2020/2452848
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spelling doaj-8c5948e06bd2485daffbf09617319cc22020-11-25T04:00:59ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09001942-09942020-01-01202010.1155/2020/24528482452848Withaferin A Exerts Preventive Effect on Liver Fibrosis through Oxidative Stress Inhibition in a Sirtuin 3-Dependent MannerJingya Gu0Chang Chen1Jue Wang2Tingting Chen3Wenjuan Yao4Tingdong Yan5Zhaoguo Liu6School of Pharmacy, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, ChinaSchool of Pharmacy, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, ChinaSchool of Pharmacy, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, ChinaSchool of Pharmacy, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, ChinaSchool of Pharmacy, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, ChinaSchool of Pharmacy, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, ChinaSchool of Pharmacy, Nantong University, 19 Qixiu Road, Nantong, Jiangsu Province 226001, ChinaSirtuin 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.http://dx.doi.org/10.1155/2020/2452848
collection DOAJ
language English
format Article
sources DOAJ
author Jingya Gu
Chang Chen
Jue Wang
Tingting Chen
Wenjuan Yao
Tingdong Yan
Zhaoguo Liu
spellingShingle Jingya Gu
Chang Chen
Jue Wang
Tingting Chen
Wenjuan Yao
Tingdong Yan
Zhaoguo Liu
Withaferin A Exerts Preventive Effect on Liver Fibrosis through Oxidative Stress Inhibition in a Sirtuin 3-Dependent Manner
Oxidative Medicine and Cellular Longevity
author_facet Jingya Gu
Chang Chen
Jue Wang
Tingting Chen
Wenjuan Yao
Tingdong Yan
Zhaoguo Liu
author_sort Jingya Gu
title Withaferin A Exerts Preventive Effect on Liver Fibrosis through Oxidative Stress Inhibition in a Sirtuin 3-Dependent Manner
title_short Withaferin A Exerts Preventive Effect on Liver Fibrosis through Oxidative Stress Inhibition in a Sirtuin 3-Dependent Manner
title_full Withaferin A Exerts Preventive Effect on Liver Fibrosis through Oxidative Stress Inhibition in a Sirtuin 3-Dependent Manner
title_fullStr Withaferin A Exerts Preventive Effect on Liver Fibrosis through Oxidative Stress Inhibition in a Sirtuin 3-Dependent Manner
title_full_unstemmed Withaferin A Exerts Preventive Effect on Liver Fibrosis through Oxidative Stress Inhibition in a Sirtuin 3-Dependent Manner
title_sort withaferin a exerts preventive effect on liver fibrosis through oxidative stress inhibition in a sirtuin 3-dependent manner
publisher Hindawi Limited
series Oxidative Medicine and Cellular Longevity
issn 1942-0900
1942-0994
publishDate 2020-01-01
description 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.
url http://dx.doi.org/10.1155/2020/2452848
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