ZFIN ID: ZDB-PUB-200403-119
Screening ginseng saponins in progenitor cells identifies 20(R)-ginsenoside Rh2 as an enhancer of skeletal and cardiac muscle regeneration
Kim, A.R., Kim, S.W., Lee, B.W., Kim, K.H., Kim, W.H., Seok, H., Lee, J.H., Um, J., Yim, S.H., Ahn, Y., Jin, S.W., Jung, D.W., Oh, W.K., Williams, D.R.
Date: 2020
Source: Scientific Reports   10: 4967 (Journal)
Registered Authors: Jin, Suk-Won, Williams, Darren W.
Keywords: none
MeSH Terms:
  • Adult
  • Animals
  • Cell Survival
  • Ginsenosides/chemistry
  • Ginsenosides/pharmacology*
  • High-Throughput Screening Assays
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal/cytology*
  • Muscle, Skeletal/drug effects
  • Muscle, Skeletal/metabolism
  • Myocardial Infarction/drug therapy*
  • Myocardial Infarction/metabolism
  • Myocardial Infarction/pathology
  • Myocardium/cytology*
  • Myocardium/metabolism
  • Panax/chemistry*
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration
  • Saponins/chemistry*
  • Stem Cells/metabolism*
  • Zebrafish
PubMed: 32188912 Full text @ Sci. Rep.
FIGURES
ABSTRACT
Aging is associated with increased prevalence of skeletal and cardiac muscle disorders, such as sarcopenia and cardiac infarction. In this study, we constructed a compendium of purified ginsenoside compounds from Panax ginseng C.A. Meyer, which is a traditional Korean medicinal plant used to treat for muscle weakness. Skeletal muscle progenitor cell-based screening identified three compounds that enhance cell viability, of which 20(R)-ginsenoside Rh2 showed the most robust response. 20(R)-ginsenoside Rh2 increased viability in myoblasts and cardiomyocytes, but not fibroblasts or disease-related cells. The cellular mechanism was identified as downregulation of cyclin-dependent kinase inhibitor 1B (p27Kip1) via upregulation of Akt1/PKB phosphorylation at serine 473, with the orientation of the 20 carbon epimer being crucially important for biological activity. In zebrafish and mammalian models, 20(R)-ginsenoside Rh2 enhanced muscle cell proliferation and accelerated recovery from degeneration. Thus, we have identified 20(R)-ginsenoside Rh2 as a p27Kip1 inhibitor that may be developed as a natural therapeutic for muscle degeneration.
ADDITIONAL INFORMATION