Tanshinone IIA and Astragaloside IV promote the angiogenesis of mesenchymal stem cell-derived endothelial cell-like cells via upregulation of Cx37, Cx40 and Cx43

Tanshinone IIA (Tan IIA) and Astragaloside IV (AGS-IV) were used as therapeutic treatments for coronary heart diseases (CHDs) in ancient China. However, the underlying mechanisms mediating the effects of Tan IIA and AGS-IV in angiogenesis remain unknown. In the present study, mesenchymal stem cells (MSCs) were induced to differentiate into endothelial cell (EC)-like cells in vitro and the effects of Tan IIA and/or AGS-IV on the functions of these cells, including cell proliferation and tube formation, were assessed. Compared with the single-agent groups (Tan IIA or AGS-IV only), combined-agent (Tan IIA and AGS-IV) treatment significantly enhanced the proliferation and tube formation capacity of EC-like cells. In addition, the expression of connexin 37 (Cx37), Cx40 and Cx43 in the combined-agent group was significantly increased compared with the single-agent groups. Furthermore, enhanced gap junctional intercellular communication (GJIC) was identified in the combined-agent group, as evidenced by increased dye transfer in scrape-loading dye transfer assays. In conclusion, Tan IIA and AGS-IV may promote the angiogenesis of EC-like cells by upregulating the expression of Cx37, Cx40 and Cx43 and enhancing GJIC function. The results of the present study may provide experimental evidence for the clinical application of Tan IIA and AGS-IV as a treatment for CHDs.