Screening ginseng saponins in progenitor cells identifies 20(R)-ginsenoside Rh2 as an enhancer of skeletal and cardiac muscle regeneration

  • Sci Rep. 2020 Mar 18;10(1):4967. doi: 10.1038/s41598-020-61491-4.
Ah Ra Kim  #  1  2 ,  Seon-Wook Kim  #  1 ,  Ba-Wool Lee  #  3 ,  Kuk-Hwa Kim  3 ,  Woong-Hee Kim  1 ,  Hong Seok  1 ,  Ji-Hyung Lee  1 ,  JungIn Um  1 ,  Soon-Ho Yim  4 ,  Youngkeun Ahn  5 ,  Suk-Won Jin  2  6 ,  Da-Woon Jung  7 ,  Won Keun Oh  8 ,  Darren R Williams  9
Affiliations
  • 1. New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Jeollanam-do, 61005, Republic of Korea.
  • 2. Developmental Genetics Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Jeollanam-do, 61005, Republic of Korea.
  • 3. Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.
  • 4. Department of Pharmaceutical Engineering, Dongshin University, Naju, Jeollanam-do, 58245, Republic of Korea.
  • 5. Cell Regeneration Research Center, Department of Cardiology, Chonnam National University Hospital/Chonnam National University Medical School, Gwangju, 61469, Republic of Korea.
  • 6. Yale Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, 06511, USA.
  • 7. New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Jeollanam-do, 61005, Republic of Korea. [email protected].
  • 8. Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea. [email protected].
  • 9. New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Jeollanam-do, 61005, Republic of Korea. [email protected].
  • # Contributed equally.
PMID: 32188912 DOI: 10.1038/s41598-020-61491-4
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.

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