Inhibitory effect of ginsenoside Rb1 on calcineurin signal pathway in cardiomyocyte hypertrophy induced by prostaglandin F2α

Aim: To examine the antihypertrophic effect of ginsenoside Rb-1 (Rb-1) induced by prostaglandin F-2 alpha(PGF(2 alpha)) in vitro and to investigate the possible mechanisms involved in the calcineurin (CaN) signal transduction pathway. Methods: The cardiomyocyte hypertrophy induced by PGF(2 alpha) and the antihypertrophic effect of Rb-1 were evaluated in primary culture by measuring the cell diameter, protein content, and atrial natriuretic peptide (ANP) mRNA expression. ANP and CaN mRNA expressions, CaN and its downstream effectors NFAT(3) and GATA(4) protein expressions, and the intracellular free Ca2+ concentration ([Ca2+](i)) were assayed by RT-PCR, Western blot, and fluorescent determination using Fura 2/AM, respectively. Results: PGF(2 alpha)(100 nmol/L) significantly increased the cardiomyocyte diameter, protein content and [Ca2+](i), and promoted ANP, CaN mRNA, and CaN/NFAT(3)/GATA(4) protein expressions, which were inhibited by either Rb-1 in a concentration-dependent manner (50,100, and 200 mu g/mL) or L-arginine (1 mmol/L). N-G-nitro-L-arginine-methyl ester, a nitric oxide synthase inhibitor, could abolish the effects of L-arginine, but failed to change the effects of Rb-1 in the experiments above. Conclusion: The present data implicate that Rb-1 attenuates cardiac hypertrophy, the underlying mechanism may be involved in the inhibition of the Ca2+-CaN signal transduction pathway.