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In this study, we constructed a compendium of purified ginsenoside compounds from<jats:italic>Panax ginseng<\/jats:italic>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(<jats:italic>R<\/jats:italic>)-ginsenoside Rh<jats:sub>2<\/jats:sub>showed the most robust response. 20(<jats:italic>R<\/jats:italic>)-ginsenoside Rh<jats:sub>2<\/jats:sub>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 (p27<jats:sup>Kip1<\/jats:sup>) 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(<jats:italic>R<\/jats:italic>)-ginsenoside Rh<jats:sub>2<\/jats:sub>enhanced muscle cell proliferation and accelerated recovery from degeneration. Thus, we have identified 20(<jats:italic>R<\/jats:italic>)-ginsenoside Rh<jats:sub>2<\/jats:sub>as a p27<jats:sup>Kip1<\/jats:sup>inhibitor that may be developed as a natural therapeutic for muscle degeneration.<\/jats:p>","DOI":"10.1038\/s41598-020-61491-4","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T12:46:08Z","timestamp":1584535568000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Screening ginseng saponins in progenitor cells identifies 20(R)-ginsenoside Rh2 as an enhancer of skeletal and cardiac muscle regeneration"],"prefix":"10.1038","volume":"10","author":[{"given":"Ah Ra","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seon-Wook","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4944-5145","authenticated-orcid":false,"given":"Ba-Wool","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuk-Hwa","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woong-Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Seok","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Hyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JungIn","family":"Um","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soon-Ho","family":"Yim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngkeun","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suk-Won","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da-Woon","family":"Jung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0761-3064","authenticated-orcid":false,"given":"Won Keun","family":"Oh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren R.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,18]]},"reference":[{"key":"61491_CR1","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1016\/S0006-2952(99)00212-9","volume":"58","author":"AS Attele","year":"1999","unstructured":"Attele, A. 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