Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside F2 enhances glucose metabolism by modulating insulin signal transduction in human hepatocarcinoma cells

  • Shengqiang Han (Institute of Translational Medicine, Medical College, Yangzhou University) ;
  • Long You (Department of Integrative Biotechnology, and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University) ;
  • Yeye Hu (School of Life Sciences, Huaiyin Normal University) ;
  • Shuai Wei (College of Food Science and Technology, Guangdong Ocean University) ;
  • Tingwu Liu (School of Life Sciences, Huaiyin Normal University) ;
  • Jae Youl Cho (Department of Integrative Biotechnology, and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University) ;
  • Weicheng Hu (Institute of Translational Medicine, Medical College, Yangzhou University)
  • Received : 2022.08.05
  • Accepted : 2022.10.11
  • Published : 2023.05.01
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Abstract

Background: Ginsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose. Methods: HepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots. Results: Cell viability assays showed that GF2 up to 50 μM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis. Conclusion: Overall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3β signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

Keywords

Acknowledgement

This study was financially supported by Natural Science Foundation of Jiangsu Province (BK20201480) and Natural Science Foundation of the Higher Education Institutions of Jiangsu Province (19KJA150003).

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