Ginseng, the root of Panax ginseng, has been used as folk medicine in the treatment of various diseases for thousands of years in China. Ginsenoside Rb-1 (Rb-1), one of the effective components of ginseng, has been reported to release nitric oxide and decrease intracellular free Ca2+ in cardiac myocytes, both of which play important roles in antihypertrophic effect. This study was to investigate the potential effect of Rb-1 on right ventricular hypertrophy (RVH) induced by monocrotaline (MCT) and its possible influence on calcineurin (CaN) signal trasnsduction pathway. MCT-treated animals were administered with Rb, (10 and 40 mg/kg) from day 1 to day 14 (preventive administration) or from day 15 to day 28 (therapeutic administration), or with vehicle as corresponding controls. After 2 weeks, significantly hypertrophic reactions, including RVH index and the expressions of atrial natriuretic peptide mRNA, appeared in right ventricle of all MCT-treated animals (p < 0.05), which were significantly decreased with some improvements of myocardial pathomorphology in both Rb-1 prevention- and therapy-groups (p < 0.05). Similarly, MCT-treatment caused the high expressions of mRNA and/or proteins of CaN, NFAT(3) and GATA(4) from cardiocytes (p < 0.05) and Rb-1 could alleviate the expressions of these factors above (p < 0.05). These results suggest that Rb-1 treatment can inhibit the RVH induced by MCT, which may be involved in its inhibitory effects on CaN signal transduction pathway. (c) 2007 Elsevier Ireland Ltd. All rights reserved.