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Ginsenoside Rg1 protects against d-galactose induced fatty liver disease in a mouse model via FOXO1 transcriptional factor.

Abstract：

AIMS:Rg1 is the most active component of traditional Chinese medicine ginseng, having anti-aging and anti-oxidative stress features in multiple organs. Cellular senescence of hepatocytes is involved in the progression of a wide spectrum of chronic liver diseases. In this study, we investigated the potential benefits and mechanism of action of Rg1 on aging-driven chronic liver diseases. MATERIALS AND METHODS:A total of 40 male C57BL/6 mice were randomly divided into four groups: control group; Rg1 group; Rg1+d-gal group; and d-gal group. Blood and liver tissue samples were collected for determination of liver function, biochemical and molecular markers, as well as histopathological investigation. KEY FINDINGS:Rg1 played an anti-aging role in reversing d-galactose induced increase in senescence-associated SA-β-gal staining and p53, p21 protein in hepatocytes of mice and sustained mitochondria homeostasis. Meanwhile, Rg1 protected livers from d-galactose caused abnormal elevation of ALT and AST in serum, hepatic steatosis, reduction in hepatic glucose production, hydrogenic degeneration, inflammatory phenomena including senescence-associated secretory phenotype (SASP) IL-1β, IL-6, MCP-1 elevation and lymphocyte infiltration. Furthermore, Rg1 suppressed drastic elevation in FOXO1 phosphorylation resulting in maintaining FOXO1 protein level in the liver after d-galactose treatment, followed by FOXO1 targeted antioxidase SOD and CAT significant up-regulation concurrent with marked decrease in lipid peroxidation marker MDA. SIGNIFICANCE:Rg1 exerts pharmaceutic effects of maintaining FOXO1 activity in liver, which enhances anti-oxidation potential of Rg1 to ameliorate SASP and to inhibit inflammation, also promotes metabolic homeostasis, and thus protects livers from senescence induced fatty liver disease. The study provides a potential therapeutic strategy for alleviating chronic liver pathology.

journal_name

Life Sci

journal_title

Life sciences

authors

Qi R,Jiang R,Xiao H,Wang Z,He S,Wang L,Wang Y

doi

10.1016/j.lfs.2020.117776

subject

Has Abstract

pub_date

2020-08-01 00:00:00

pages

117776

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(20)30524-5

journal_volume

254

pub_type

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