20(S)-ginsenoside Rg3 promotes myoblast differentiation and protects against myotube atrophy via regulation of the Akt/mTOR/FoxO3 pathway

Biochem Pharmacol. 2020 Oct:180:114145. doi: 10.1016/j.bcp.2020.114145. Epub 2020 Jul 10.

Abstract

We previously found that 20(S)-ginsenoside Rg3 (S-Rg3) promotes myoblast differentiation via an unknown mechanism. Here we measured levels of myosin heavy chain (MHC) and myogenin, markers of myoblast differentiation, using Western blot analysis and immunofluorescence staining. Notably, S-Rg3 treatment of C2C12 myoblasts led to increased muscle differentiation and protection from muscle atrophy in a dexamethasone (DEX)-treated C2C12 myotube-based muscle atrophy model. This effect was likely caused by S-Rg3 treatment-induced promotion of Akt/mTOR phosphorylation and inhibition of FoxO3 nuclear transcription. Additionally, S-Rg3 treatment also led to increased fruit fly climbing distances (Drosophila melanogaster) and prevented muscle atrophy in aged fruit flies. Our study provides a mechanistic framework for understanding how S-Rg3 enhances myoblast differentiation and inhibits myotube atrophy through activation of the Akt/mTOR/FoxO3 signaling pathway, as demonstrated in vitro in C2C12 cells and in vivo in fruit flies.

Keywords: 20(S)-ginsenoside Rg3; Akt/mTOR/FoxO3; Myoblast differentiation; Myotube atrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Line
  • Dose-Response Relationship, Drug
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Forkhead Box Protein O3 / metabolism*
  • Ginsenosides / pharmacology*
  • Mice
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism*
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / pathology
  • Muscular Atrophy / prevention & control
  • Myoblasts / drug effects
  • Myoblasts / metabolism*
  • Nuclear Matrix-Associated Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology

Substances

  • Drosophila Proteins
  • Forkhead Box Protein O3
  • Ginsenosides
  • Mtor protein, Drosophila
  • Nuclear Matrix-Associated Proteins
  • ginsenoside Rg3
  • Proto-Oncogene Proteins c-akt