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γ-Mangostin alleviates liver fibrosis through Sirtuin 3-superoxide-high mobility group box 1 signaling axis
- Source :
- Toxicology and applied pharmacology. 363
- Publication Year :
- 2018
-
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.
- Subjects :
- 0301 basic medicine
Male
food.ingredient
SIRT3
Xanthones
Drug Evaluation, Preclinical
Toxicology
HMGB1
medicine.disease_cause
Liver Cirrhosis, Experimental
Cell Line
Garcinia mangostana
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
food
Superoxides
Sirtuin 3
medicine
Animals
Humans
HMGB1 Protein
RNA, Small Interfering
Autocrine signalling
Carbon Tetrachloride
Pharmacology
biology
Superoxide
Cell biology
Mice, Inbred C57BL
Oxidative Stress
030104 developmental biology
Treatment Outcome
chemistry
Liver
030220 oncology & carcinogenesis
Gene Knockdown Techniques
Sirtuin
biology.protein
Hepatic stellate cell
Oxidative stress
Signal Transduction
Subjects
Details
- ISSN :
- 10960333
- Volume :
- 363
- Database :
- OpenAIRE
- Journal :
- Toxicology and applied pharmacology
- Accession number :
- edsair.doi.dedup.....d714bb9177b2a0c7385f811a91eaebcd