The possible effects of
tanshinone VI (tsh), a
diterpene from the root of Tan-Shen (Salvia miltiorrhiza, Bunge (Labiatae)) on
hypertrophy and
fibrosis in cultured neonatal rat cardiac myocytes and fibroblasts were examined. Tsh had no significant effect on
protein synthesis, which was evaluated by [3H]-
leucine incorporation into the
acid insoluble fraction in the cells, in the absence of stimulatory factors in cardiac myocytes. The amount of
protein produced in cardiac myocytes was increased by 10(-8) M
endothelin-1 (ET-1), 10(-6) M
phenylephrine (PE), or 10(-8) M
insulin-like growth factor-1 (IGF-1), suggesting that
hypertrophy of cardiac myocytes in vitro was induced by these factors. The ET-1-, PE-, or IGF-1-induced increase in
protein synthesis was attenuated by treatment with 10(-5) M tsh. Treatment with 10(-5) M tsh significantly decreased the synthesis of
collagen by cardiac fibroblasts, which was evaluated by [3H]-
proline incorpolation into
acid-insoluble fraction of the fiblobrasts, in the absence of stimulatory factors for the production.
Fetal bovine serum (FBS) or
IGF-1 increased
collagen synthesis in a concentration-dependent manner. The increase at 5% FBS or 10(-8) M
IGF-1 was inhibited by 10(-5) M tsh. Fibroblast-
conditioned medium (FB-CM) increased
protein synthesis in cardiac myocytes in a concentration-dependent manner (10; - 100 %). Tsh attenuated the FB-CM-induced increase in
protein synthesis by cardiac myocytes. These results show that tsh may attenuate the humoral factor-induced
hypertrophy of cardiac myocytes and
fibrosis of cardiac fibroblasts. The findings suggest that tsh may improve the development of cardiac remodeling under pathophysiological conditions. Abbreviations.
ANP:
atrial natriuretic peptide DMEM:Dulbecco-modified Eagle's medium ET-1:
endothelin-1 FB-CM:fibroblast-
conditioned medium FBS:
fetal bovine serum IGF-1:
insulin-like growth factor-1 PE:
phenylephrine tsh:
tanshinone VI