Protective effect of ginkgolide B against isoproterenol-induced chronic heart failure in rats via modulation of Nrf2 and HO-1 signaling pathways

摘要

Purpose: To determine the protective effect of ginkgolide B (GB) against isoproterenol (ISO)-induced chronic heart failure in a rat model. Methods: A total of 32 male Wistar rats were randomly divided into 4 groups. Rats in control group received only saline, while rats in GB alone group were injected with GB at a dose of 20 mg/kg body weight (bwt) intraperitoneally (i.p). Another group of rats was injected with ISO subcutaneously (s.c.) at a dose of 85 mg/kg for 2 days (ISO group). Rats in the GB+ISO group were administered GB at a dose of 20 mg/kg, i.p., for 7 days prior to exposure to ISO s.c. at a dose of 85 mg/kg. Results: Rats pre-treated with GB for 7 days prior to ISO exposure showed a significant decrease in cardiac infarct size, and marked decreases in the levels of cardiac biomarkers, inflammatory and apoptotic biomarkers, and lipid peroxidation (p 0.05), but significant improvement in the levels of endogenous antioxidants (p 0.05). In addition, GB administration resulted in marked increases in the protein ex pression levels of heme oxygenase-1 (HO-1) and Nrf2 in cardiac tissue (p 0.05). Conclusion: These results indicate that pre-treatment of chronic heart failure rats with GB for 7 consecutive days considerably lowered inflammatory and apoptotic markers via upregulation of Nrf2/HO-1 signaling pathway. Thus, GB has cardioprotective potential in humans.