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gamma-Mangostin alleviates liver fibrosis through Sirtuin 3-superoxide-high mobility group box 1 signaling axis
Wang A1; Zhou F2; Li D2; Lu JJ2; Wang Y2; Lin L3
2019
Source PublicationTOXICOLOGY AND APPLIED PHARMACOLOGY
ISSN0041-008X
Volume363Pages:142-153
Abstract

The activation of hepatic stellate cells (HSCs) plays a critical role in liver fibrosis. In the current study, γ-mangostin (γ-man), one of the major xanthones from mangosteen (Garcinia mangostana), was found to alleviate fibrogenesis in human immortalized HSCs (LX-2 cells) and in liver from chronic carbon tetrachloride (CCl4) injured mice. γ-Man suppressed the expression levels of collagen I and α-smooth muscle actin (α-SMA) in LX-2 cells in both dose and time dependent manners. Furthermore, γ-man inhibited NAD(P)H oxidase activity through induction of sirtuin 3 (SIRT3), resulting in reduced intracellular oxidative stress in LX-2 cells. Moreover, γ-man stimulated the expression of histone deacetylase 1, which in turn decreased the acetylation and cytoplasmic shuttling of high mobility group box 1 (HMGB1), to impair autocrine HMGB1-induced HSC activation. In CCl4-injured mice, γ-man enhanced the expression of SIRT3 and decreased the expression of HMGB1, resulting in decreased accumulation of collagen I and α-SMA in liver. Consequently, γ-man might be a potent candidate to treat oxidative stress induced liver fibrosis.

KeywordSuperoxide Gamma-mangostin Fibrogenesis Sirtuin 3 Liver Fibrosis Hmgb1
DOI10.1016/j.taap.2018.11.011
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy ; Toxicology
WOS SubjectPharmacology & Pharmacy ; Toxicology
WOS IDWOS:000457068000015
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorLin L
Affiliation1.Guangdong-Macau Traditional Chinese Medicine Technology Industrial Park Development Co., Ltd, Hengqin New Area, Zhuhai, Guangdong 519031, China; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau
3.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Wang A,Zhou F,Li D,et al. gamma-Mangostin alleviates liver fibrosis through Sirtuin 3-superoxide-high mobility group box 1 signaling axis[J]. TOXICOLOGY AND APPLIED PHARMACOLOGY,2019,363:142-153.
APA Wang A,Zhou F,Li D,Lu JJ,Wang Y,&Lin L.(2019).gamma-Mangostin alleviates liver fibrosis through Sirtuin 3-superoxide-high mobility group box 1 signaling axis.TOXICOLOGY AND APPLIED PHARMACOLOGY,363,142-153.
MLA Wang A,et al."gamma-Mangostin alleviates liver fibrosis through Sirtuin 3-superoxide-high mobility group box 1 signaling axis".TOXICOLOGY AND APPLIED PHARMACOLOGY 363(2019):142-153.
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