Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside Rg5 promotes muscle regeneration via p38MAPK and Akt/mTOR signaling

  • Ryuni Kim (Drug Information Research Institute, Muscle Physiome Research Center, College of Pharmacy, Sookmyung Women's University) ;
  • Jee Won Kim (Drug Information Research Institute, Muscle Physiome Research Center, College of Pharmacy, Sookmyung Women's University) ;
  • Hyerim Choi (Drug Information Research Institute, Muscle Physiome Research Center, College of Pharmacy, Sookmyung Women's University) ;
  • Ji-Eun Oh (Department of Biomedical Laboratory Science, Far East University) ;
  • Tae Hyun Kim (Drug Information Research Institute, Muscle Physiome Research Center, College of Pharmacy, Sookmyung Women's University) ;
  • Ga-Yeon Go (Research Institute of Aging Related Disease, AniMusCure Inc.) ;
  • Sang-Jin Lee (Research Institute of Aging Related Disease, AniMusCure Inc.) ;
  • Gyu-Un Bae (Drug Information Research Institute, Muscle Physiome Research Center, College of Pharmacy, Sookmyung Women's University)
  • Received : 2022.10.26
  • Accepted : 2023.06.12
  • Published : 2023.11.01
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Abstract

Background: Skeletal muscles play a key role in physical activity and energy metabolism. The loss of skeletal muscle mass can cause problems related to metabolism and physical activity. Studies are being conducted to prevent such diseases by increasing the mass and regeneration capacity of muscles. Ginsenoside Rg5 has been reported to exhibit a broad range of pharmacological activities. However, studies on the effects of Rg5 on muscle differentiation and growth are scarce. Methods: To investigate the effects of Rg5 on myogenesis, C2C12 myoblasts were induced to differentiate with Rg5, followed by immunoblotting, immunostaining, and qRT-PCR for myogenic markers and promyogenic signaling (p38MAPK). Immunoprecipitation confirmed that Rg5 increased the interaction between MyoD and E2A via p38MAPK. To investigate the effects of Rg5 on prevention of muscle mass loss, C2C12 myotubes were treated with dexamethasone to induce muscle atrophy. Immunoblotting, immunostaining, and qRT-PCR were performed for myogenic markers, Akt/mTOR signaling for protein synthesis, and atrophy-related genes (Atrogin-1 and MuRF1). Results: Rg5 promoted C2C12 myoblast differentiation through phosphorylation of p38MAPK and MyoD/E2A heterodimerization. Furthermore, Rg5 stimulated C2C12 myotube hypertrophy via phosphorylation of Akt/mTOR. Phosphorylation of Akt induces FoxO3a phosphorylation, which reduces the expression of Atrogin-1 and MuRF1. Conclusion: This study provides an understanding of how Rg5 promotes myogenesis and hypertrophy and prevents dexamethasone-induced muscle atrophy. The study is the first, to the best of our knowledge, to show that Rg5 promotes muscle regeneration and to suggest that Rg5 can be used for therapeutic intervention of muscle weakness and atrophy, including cancer cachexia.

Keywords

Acknowledgement

The present study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP; grant no. NRF-2021-COMPA-0101, NRF-2020-R1A2C1007555, NRF-2022-R1A5A2021216).

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