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γ-Mangostin alleviates liver fibrosis through Sirtuin 3-superoxide-high mobility group box 1 signaling axis
Wang A.1,2; Zhou F.2; Li D.2; Lu J.-J.2; Wang Y.2; Lin L.2,3
2019-01-15
Source PublicationToxicology and Applied Pharmacology
ISSN10960333 0041008X
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 (CCl) 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 CCl-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.

KeywordFibrogenesis Hmgb1 Liver Fibrosis Sirtuin 3 Superoxide Γ-mangostin
DOI10.1016/j.taap.2018.11.011
URLView the original
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
Affiliation1.Guangdong Macau Tradit Chinese Med Technol Ind Pk, Hengqin New Area, Zhuhai 519031, Guangdong, Peoples R China
2.University of Macau
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Wang A.,Zhou F.,Li D.,et al. γ-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 J.-J.,Wang Y.,&Lin L..(2019).γ-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."γ-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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