Acta Pharmacologica Sinica 2007 August; 28 (8): 1149-1154; doi: 10.1111/j.1745-7254.2007.00601.x

Aim: To examine the antihypertrophic effect of ginsenoside Rb₁ (Rb₁) induced by prostaglandin F_2α (PGF_2α) in vitro and to investigate the possible mechanisms involved in the calcineurin (CaN) signal transduction pathway.

Methods: The cardiomyocyte hypertrophy induced by PGF_2α and the antihypertrophic effect of Rb₁ 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 NFAT₃ and GATA₄ 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_2α (100 nmol/L) significantly increased the cardiomyo-cyte diameter, protein content and [Ca²⁺]_i, and promoted ANP, CaN mRNA, and CaN/NFAT₃/GATA₄ protein expressions, which were inhibited by either Rb₁ in a concentration-dependent manner (50, 100, and 200 µg/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 Rb₁ in the experiments above.

Conclusion: The present data implicate that Rb₁ attenuates cardiac hypertrophy, the underlying mechanism may be involved in the inhibition of the Ca²⁺-CaN signal transduction pathway.

Keywords: Rb₁; prostaglandin F_2α; cardiac hypertrophy; calcineurin