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

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

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. jung@gist.ac.kr.
  • 8 Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea. wkoh1@snu.ac.kr.
  • 9 New Drug Targets Laboratory, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Jeollanam-do, 61005, Republic of Korea. darren@gist.ac.kr.
  • # 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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