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Ginsenoside Rg3 Upregulates Myotube Formation and Mitochondrial Function, Thereby Protecting Myotube Atrophy Induced by Tumor Necrosis Factor-Alpha

Ginsenoside Rg3 Upregulates Myotube Formation and Mitochondrial Function, Thereby Protecting Myotube Atrophy Induced by Tumor Necrosis Factor-Alpha

Sang-Jin Lee, Ju Hyun Bae, Hani Lee, Hyunji Lee, Jongsun Park, Jong-Sun Kang, Gyu-Un Bae

J Ethnopharmacol. 2019 Oct 5;242:112054.

PMID: 31271820

Abstract:

Ethnopharmacological relevance:
Ginsenoside Rg3 from Panax ginseng has reported to have multiple pharmacological activities including anti-diabetics, anti-inflammation and anti-cancer. However, the effect of ginsenoside Rg3 on myogenic differentiation and muscle atrophy is unknown.
Aim to the study:
In this study, we investigated the myogenic effect and underlying molecular mechanisms of ginsenoside Rg3 on myotube atrophy induced by tumor necrosis factor-α (TNF-α).
Materials and methods:
C2C12 myoblasts were induced to differentiate for one day followed by the treatment of TNF-α along with vehicle or ginsenoside Rg3 for additional 2 days and subjected to immunoblotting, immunocytochemistry, quantitative RT-PCR and biochemical analysis for mitochondrial function.
Results:
Ginsenoside Rg3 promotes myogenic differentiation and multinucleated myotube formation through Akt activation in a dose-dependent manner, without any cytotoxicity. Ginsenoside Rg3 treatment restores myotube formation and increases myotube diameters under TNF-α-treated conditions. Ginsenoside Rg3 enhances Akt/mTOR (mammalian target of rapamycin) signaling that in turn stimulates muscle-specific gene expression such as myosin heavy chain (MHC) and Myogenin, and suppresses the expression of muscle-specific ubiquitin ligases. In addition, ginsenoside Rg3 in TNF-α-treated myotubes significantly inhibits the production of mitochondrial ROS and restores mitochondrial membrane potential (MMP) and ATP contents. Furthermore, ginsenoside Rg3 upregulates the activities and expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and the mitochondrial biogenetic transcription factors, nuclear respiratory factor-1 (NRF1) and mitochondrial transcription factor A (Tfam) in TNF-α-induced myotube atrophy.
Conclusions:
This study provides a mechanistic insight into the effect of ginsenoside Rg3 on myogenic differentiation and myotube atrophy, suggesting that ginsenoside Rg3 has a promising potential as a therapeutic or neutraceutical remedy to intervene muscle weakness and atrophy.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP14197605	Ginsenoside Rg3		14197-60-5	Price

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