Sodium tanshinone IIA sulfonate derived from Danshen (Salvia miltiorrhiza) attenuates hypertrophy induced by angiotensin II in cultured neonatal rat cardiac cells

Abstract

Sodium tanshinone IIA sulfonate (STS), a derivative of tanshinone IIA, is isolated from the root of Salvia miltiorrhiza known as "Danshen." Although injection of S. miltiorrhiza extract and STS is used widely and successfully in clinics in China for treating cardiovascular diseases, the exact mechanism for its therapeutic basis is poorly understood. The present study was undertaken to characterize the effect of STS on angiotensin II-induced hypertrophy on cultured myocytes and cardiac fibroblasts (nonmyocytes) prepared from neonatal rat hearts. Angiotensin II (1nM) increased protein synthesis and surface area in myocytes, and DNA synthesis and cell number in nonmyocytes, respectively. Exposure of the myocytes to STS (5-80 microM) for 24hr produced no cytotoxicity as evaluated by the 3-[4,5-dimethylthiazol-2-yl]-3,5-diphenylformazan (MTT) assay. Although STS (10 microM) alone showed no effect on the growth of cultured cardiac cells, it markedly suppressed angiotensin II-induced enlargement of cells and [3H]phenylalanine incorporation, proceeding from the induction of immediate early gene (c-jun) expression in myocytes. Furthermore, STS prevented the rise in [Ca(2+)](i) mediated by angiotensin II in myocytes. In contrast, STS (10 microM) was without effect on hyperplasia and c-jun expression induced by angiotensin II in nonmyocytes. The present in vitro findings support the interpretation that STS is a substance that may be beneficial in protecting the myocardium against hypertrophy.