{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:27:59Z","timestamp":1785403679955,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T00:00:00Z","timestamp":1777161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2023A1515111039"],"award-info":[{"award-number":["2023A1515111039"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Natural Science Basic Research Program of Shaanxi","award":["2025JC-QYCX-021"],"award-info":[{"award-number":["2025JC-QYCX-021"]}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"crossref","award":["2023A1515010460"],"award-info":[{"award-number":["2023A1515010460"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81560056"],"award-info":[{"award-number":["81560056"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["81560056"],"award-info":[{"award-number":["81560056"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Foundation Central Guiding Local Science and Technology Development Fund","award":["2024ZY01009"],"award-info":[{"award-number":["2024ZY01009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Salvia miltiorrhiza Bunge has been used traditionally for cardiovascular disorders, but its specific roles in stem cell cardiac differentiation remain unclear. In this study, we examined whether Salvia miltiorrhiza Bunge (SM) promotes cardiomyocyte differentiation from mouse embryonic stem cells (mESCs) and defined its underlying mechanism. To dynamically monitor cardiac differentiation, we established a Tnnt2-H2B-mCherry reporter mESC line that retained normal pluripotency and differentiation capacity. Using an embryoid body-based differentiation system, we found that SM exerted a distinct temporal effect on lineage progression: treatment during the early differentiation window inhibited pluripotency maintenance, proliferation, and mesodermal development, whereas administration during the cardiac precursor stage markedly enhanced cardiomyocyte formation, as indicated by increased beating embryoid bodies and upregulation of Isl1, Nkx2.5, Tnnt2, Myh6, and Myl7. Mechanistically, transcriptomic and protein analyses showed that SM suppressed canonical Wnt\/\u03b2-catenin signaling, including downregulation of Dvl2, \u03b2-catenin, Axin2, c-Myc, and Cyclin D1, while Wnt activation WAY262611 partially reversed these effects. Further compound screening identified tanshinone IIA (Tan IIA) as the principal active constituent of SM, which largely recapitulated the pro-cardiogenic and Wnt-inhibitory effects of the crude extract. Together, these findings identify SM and Tan IIA as stage-dependent regulators of mESC fate and support their potential utility in natural product-based strategies for improving stem cell-derived cardiomyocyte generation.<\/jats:p>","DOI":"10.3390\/cells15090786","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:32:22Z","timestamp":1777469542000},"page":"786","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Salvia miltiorrhiza Bunge Regulates the Differentiation of mESCs into Cardiomyocytes via the Wnt\/\u03b2-Catenin Signaling Pathway"],"prefix":"10.3390","volume":"15","author":[{"given":"Guotao","family":"Lu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"},{"name":"Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A & F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"},{"name":"Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A & F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ren","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"},{"name":"Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A & F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Development and Utilization of Forest Food Resources, Zhejiang University, Hangzhou 311300, China"},{"name":"Zhejiang Shouxiangu Pharmaceutical Co., Ltd., Wuyi 321200, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4269-128X","authenticated-orcid":false,"given":"Fan","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China"},{"name":"Shaanxi Centre of Stem Cells Engineering & Technology, Northwest A & F University, Yangling 712100, China"},{"name":"Shenzhen Research Institute, Northwest A&F University, Shenzhen 518057, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e029971","DOI":"10.1161\/JAHA.123.029971","article-title":"Acute Myocardial Infarction: Etiologies and Mimickers in Young Patients","volume":"12","author":"Krittanawong","year":"2023","journal-title":"J. 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