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Updated: Feb 1, 2026

A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia
Published on: February 3, 2023
γ-Mangostin alleviates liver fibrosis through Sirtuin 3-superoxide-high mobility group box 1 signaling axis
Anqi Wang1, Fayang Zhou2, Dan Li2
1Guangdong-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, University of Macau, Avenida da Universidade, Taipa, Macau 999078, China.
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.
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