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Measurement of Fatty Acid β-Oxidation in a Suspension of Freshly Isolated Mouse Hepatocytes
Published on: September 9, 2021
Ginsenoside Rg1 protects against d-galactose induced fatty liver disease in a mouse model via FOXO1 transcriptional
Rongjia Qi1, Rong Jiang1, Hanxianzhi Xiao1
1Lab of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Medical University, Chongqing 400016, China.
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.
Insights
Ginsenoside Rg1 from traditional Chinese medicine ginseng reverses aging-related liver damage by reducing inflammation and oxidative stress. This study highlights Rg1 as a potential therapy for chronic liver diseases and fatty liver.
Area of Science:
- Hepatology
- Gerontology
- Pharmacology
Background:
- Cellular senescence in hepatocytes contributes to chronic liver disease progression.
- Ginsenoside Rg1 (Rg1), a key component of ginseng, exhibits anti-aging and antioxidant properties.
- Investigating Rg1's effects on aging-related liver pathology is crucial.
Purpose of the Study:
- To explore the protective effects and underlying mechanisms of Rg1 against aging-induced chronic liver injury.
- To evaluate Rg1's potential in mitigating liver senescence and dysfunction.
Main Methods:
- Male C57BL/6 mice were assigned to control, Rg1, Rg1+d-galactose, or d-galactose groups.
- Evaluated liver function, oxidative stress markers, senescence markers (SA-β-gal, p53, p21), inflammation (SASP), and lipid metabolism.
- Histopathological analysis and molecular marker assessment were performed on liver tissues and serum.
Main Results:
- Rg1 reversed d-galactose-induced hepatocyte senescence and maintained mitochondrial homeostasis.
- Rg1 normalized liver enzymes (ALT, AST), reduced hepatic steatosis, and prevented glucose production decline.
- Rg1 ameliorated inflammation by suppressing SASP factors and maintained FOXO1 activity, upregulating antioxidases (SOD, CAT) and decreasing MDA.
Conclusions:
- Rg1 protects the liver from senescence-induced damage by maintaining FOXO1 activity, enhancing antioxidant capacity, and promoting metabolic homeostasis.
- Rg1 effectively mitigates inflammation and senescence-associated secretory phenotype (SASP).
- Rg1 represents a promising therapeutic strategy for managing chronic liver diseases and age-related liver pathology.

