Tanshinone VI Induces Cardiac Differentiation of Cardiosphere-Derived Cells Prepared from Rat Hearts

Cell transplantation therapy is a promising new treatment for myocardial infarction and heart failure. Developing methods to promote the engraftment of cardiac stem cells into cardiac tissue and their differentiation into cardiac cells is a strategy for improving the efficacy of cell transplantation therapy. Tanshinone VI (TanVI), a component extracted from the roots of Salvia miltiorrhiza Bunge (Labiatae), is a possible pharmacological agent for ischemic heart disease. However, since the effects of TanVI on the differentiation of cardiac stem cells remain unclear, we examined the effects of TanVI on the cardiac differentiation potential of cardiac stem cells. Cardiosphere-derived cells (CDCs), the cardiac stem/progenitor cells, were prepared from adult rat hearts. After CDCs were cultured in the presence of TanVI, cell numbers, expression of cardiomyocyte markers, and intracellular signaling protein levels involved in the differentiation into cardiomyocytes were measured. Treatment of CDCs with TanVI inhibited the increase in cell numbers and induced their expression of cardiomyocyte marker proteins. TanVI treatment also inhibited the Akt/glycogen synthase kinase 3β (GSK3β)/β-catenin and c-Raf/MEK1/2/extracellular signal-regulated kinase 1/2 (ERK1/2) pathways. We found that TanVI promotes cardiac differentiation of CDCs. Our findings also suggest that inhibition of the Akt/GSK3β/β-catenin pathway and the c-Raf/MEK1/2/ERK1/2 pathway may contribute to the differentiation from CDCs to cardiomyocytes. TanVI may play an adjunctive role in cardiac stem cell transplantation therapy.