Ginkgolide A protects adverse cardiac remodeling through enhancing antioxidation and nitric oxide utilization in mice with pressure overload.

In this study, we aimed to explore whether ginkgolide A (GA) would exhibit cardio-protective effects in mice with pressure overload through enhancing antioxidation and nitric oxide (NO) bioavailability. 21 male mice were randomly assigned into three groups as follows: sham group (10 ml/kg/day PBS, n=7), transverse aortic constriction (TAC) group (TAC and 10 ml/kg/day PBS, n=7) and GA group (TAC and 20 mg/kg/day GA, n=7). All groups received an intraperitoneal injection for four weeks. Heart and body mass were measured. Cardiac function was assessed by echocardiography. The collagen deposition, area of cardiomyocytes, number of capillaries and cell apoptosis were evaluated using Masson's staining, WGA staining, CD31 staining and TUNEL assay, respectively. Cadiac oxidative and antioxidative indexes were measured by colorimetry. Nitrotyrosine (NT) and transforming growth factor-β (TGF-β) were determined by ELISA. Phospho-endothelial NO synthases (eNOS) (Ser1177), phospho-eNOS (Thr 495), eNOS, neuronal NOS (nNOS), inducible NOS (iNOS) and GAPDH were analyzed by western blot. GA treatment greatly improved cardiac dysfunction, suppressed cardiac hypertrophy and increased capillary number at 4 weeks after TAC (P<0.05). Fibrotic area, cardiomyocyte area, and cell apoptosis of GA group were declined notably as compared to those of TAC group (P<0.05). GA administration substantially attenuated cardiac oxidative stress, and reduced NT and TGF-β levels (P<0.05). Besides, GA medication can enhance eNOS signaling, resulting in increased cardiac NO production (P<0.05). GA had a cardioprotective effect in mice with pressure overload, which was closely related with reducing oxidative stress and enhancing NO bioavailability in hearts.