Ginsenoside Rg5 inhibits lipid accumulation and hepatocyte apoptosis via the Notch1 signaling pathway in NASH mice

Na Li; Chenhui Zhu; Rongzhan Fu; Xiaoxuan Ma; Zhiguang Duan; Daidi Fan

doi:10.1016/j.phymed.2023.155287

Ginsenoside Rg5 inhibits lipid accumulation and hepatocyte apoptosis via the Notch1 signaling pathway in NASH mice

Phytomedicine. 2024 Feb:124:155287. doi: 10.1016/j.phymed.2023.155287. Epub 2023 Dec 16.

Authors

Na Li¹, Chenhui Zhu¹, Rongzhan Fu¹, Xiaoxuan Ma¹, Zhiguang Duan², Daidi Fan³

Affiliations

¹ Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an 710069, China; Biotech & Biomed Research Institute, Northwest University, 229 North Taibai Road, Xi'an 710069, China.
² Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an 710069, China; Biotech & Biomed Research Institute, Northwest University, 229 North Taibai Road, Xi'an 710069, China. Electronic address: duanzhiguang@nwu.edu.cn.
³ Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, China; Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi'an 710069, China; Biotech & Biomed Research Institute, Northwest University, 229 North Taibai Road, Xi'an 710069, China. Electronic address: fandaidi@nwu.edu.cn.

PMID: 38176268
DOI: 10.1016/j.phymed.2023.155287

Abstract

Background: Non-alcoholic steatohepatitis (NASH) is a prevalent chronic liver disease that lacks an FDA-approved treatment medicine. Despite the known antitumor and hypoglycemic properties of Ginsenoside Rg5, its effects and underlying mechanisms in the context of NASH remain largely unexplored.

Purpose: This study aims to investigate the effect of Rg5 on NASH mice induced by a high-fat diet and CCl₄.

Study design: In vivo experiments, a mouse NASH model was established by a HFHC diet plus intraperitoneal injection of low-dose CCl₄. In vitro experiments, a cellular steatosis model was established using free fatty acids (FFA) induced HepG2 cells. In addition, a fibrogenesis model was established using HSC-LX2 cells.

Methods: The effects of Ginsenoside Rg5 on lipid accumulation and oxidative damage were analyzed by ELISA kit, H&E staining, Oil Red O staining, flow cytometry and Western blot. The effects of Ginsenoside Rg5 on liver fibrosis were analyzed by Masson staining, Sirus Red staining, immunohistochemistry and Western blot. The effect of Ginsenoside Rg5 on Notch1 signaling pathway in liver was studied by protein Oil Red staining, protein immunoblotting and immunofluorescence.

Results: In terms of lipid accumulation, Rg5 has the ability to regulate key proteins related to lipogenesis, thereby inhibiting hepatic lipid accumulation and oxidative stress. Additionally, Rg5 can reduce the occurrence of hepatocyte apoptosis by regulating the p53 protein. Moreover, after Rg5 intervention, the presence of fibrotic proteins (α-SMA, Collagen 1, TGF-β) in the liver is significantly suppressed, thus inhibiting liver fibrosis. Lastly, Rg5 leads to a decrease in the expression levels of Notch1 and its ligand Jagged-1 in the liver.

Conclusion: In summary, the regulatory effects of Rg5 on the Notch1 signaling pathway play a crucial role in modulating hepatic lipid metabolism and preventing hepatocyte apoptosis, thereby impeding the progression of NASH. These findings highlight the potential of Rg5 as a promising natural product for interventions targeting NASH.

Keywords: Lipid accumulation; Liver fibrosis; NASH; Notch1; Rg5.

MeSH terms

Animals
Apoptosis
Diet, High-Fat / adverse effects
Disease Models, Animal
Ginsenosides*
Hep G2 Cells
Humans
Lipids
Liver
Liver Cirrhosis / metabolism
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease* / metabolism
Signal Transduction

Substances

ginsenoside Rg5
Lipids
Ginsenosides