Ginsenoside Rg1 Protects against Non-alcoholic Fatty Liver Disease by Ameliorating Lipid Peroxidation, Endoplasmic Reticulum Stress, and Inflammasome Activation.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. The purpose of this study is to investigate the protective effects of ginsenoside Rg1 (Rg1), an active ingredient of a natural medicine, and further clarify its protective mechanisms, in a mouse model of NAFLD induced by a high-fat diet. Rg1 significantly reduced liver weight, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), liver free fatty acids (FFAs) and malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD) activity. Rg1 also upregulated the expression of peroxisome proliferator-activated receptor-alpha (PPARα), which stimulated fatty acid beta oxidation and promoted the metabolism of FFAs and TG. It also suppressed the expression of CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), cysteine-containing aspartate-specific proteases 12 (Caspase 12), and glucose-regulated protein78 (GRP78), which reduced endoplasmic reticulum (ER) stress. Furthermore, Rg1 alleviated liver inflammation by inhibiting the activation of nucleotide binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) and thus reduced the production of inflammatory cytokines, such as interleukin 1-beta (IL-1β) and interleukin 18 (IL-18). These results suggested that Rg1 may protect against NAFLD, through regulation of lipid peroxidation, ER stress and inflammasome activation.

• Authors: Yashu Xu, Cheng Yang, Shujun Zhang, Jiajun Li, Qing Xiao, Wenxiang Huang
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 41 Issue 11 Pg. 1638-1644 (Nov 01 2018) ISSN: 1347-5215 [Electronic] Japan
• PMID: 30135326 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• CCAAT-Enhancer-Binding Proteins
• CEBPA protein, mouse
• Cytokines
• Endoplasmic Reticulum Chaperone BiP
• Ginsenosides
• Heat-Shock Proteins
• Hspa5 protein, mouse
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• PPAR alpha
• Caspase 12
• ginsenoside Rg1

Topics

• Animals
• Antioxidants (metabolism, pharmacology, therapeutic use)
• CCAAT-Enhancer-Binding Proteins (metabolism)
• Caspase 12 (metabolism)
• Cytokines (metabolism)
• Diet, High-Fat (adverse effects)
• Disease Models, Animal
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress (drug effects)
• Female
• Ginsenosides (pharmacology, therapeutic use)
• Heat-Shock Proteins (metabolism)
• Inflammasomes (metabolism)
• Inflammation (etiology, metabolism, prevention & control)
• Lipid Metabolism (drug effects)
• Lipid Peroxidation (drug effects)
• Liver (drug effects, enzymology, metabolism)
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Non-alcoholic Fatty Liver Disease (etiology, metabolism, prevention & control)
• PPAR alpha (metabolism)
• Panax (chemistry)
• Phytotherapy