Myocardial hypertrophy is a crucial pathological change that occurs during post-anthracycline treatment cardiomyopathy. The effects of ginsenoside Rb1 (Rb1) on anthracycline-induced hypertrophy remain unclear. This study aimed to explore the antihypertrophic effect of Rb1 on post-doxorubicin (DOX) treatment myocardial hypertrophy and underlying mechanism.

Post-DOX treatment myocardial hypertrophy was induced 12 days or 22 h after 15 mg/kg DOX injection in C57BL/6 mice or 2 h DOX (2 μM) incubation in H9c2 cardiomyoblasts. Rb1 was administered 2 days before DOX exposure for 14 consecutive days or 6 h before DOX incubation for 30 h. Heart weight/Body weight (HW/BW), heart weight/tibia length (HW/TL) ratios, echocardiography, WGA staining and the contents of α-SMA, BNP and β-MCH were used to validate myocardial hypertrophy. HE staining, Masson staining, and transmission electron microscopy were performed to assess changes in cardiac morphology. Fluo-3/AM fluorescence was applied to measure the cytosolic free calcium concentration. Western blot, immunohistochemical and immunofluorescence staining were used to assess the expression of CaNBβ/NFATc4/GATA4 signaling.

Rb1 significantly decreased the HW/BW, HW/TL and LVd mass/BW ratios, reduced the cardiomyocyte area and the expression of BNP, β-MHC and α-SMA. Rb1 also relieved myocardial fibrosis and subcellar structure changes and improved the cardiac hemodynamics of post-DOX treatment mice. Rb1 decreased post-DOX treatment calcium overload. Consistent with these findings, in vivo and in vitro CaN, NFATc4 and GATA4 overexpression was rectified.

Rb1 ameliorated post-doxorubicin treatment myocardial hypertrophy, which may be correlated with CaN/NFAT/GATA4 downregulation.

Ginsenoside Rb1

Post-doxorubicin treatment

Myocardial hypertrophy

Fibrosis

CaN/NFATc4/GATA4

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