Ginkgo biloba extract and Aspirin synergistically attenuate activated platelet-induced ROS production and LOX-1 expression in human coronary artery endothelial cells

Abstract

AimIn the present study, we investigated whether the therapeutic dosages of Ginkgo biloba extract (EGb) and Aspirin (ASP) might synergistically suppress oxidative stress through regulating the expressions of LOX-1 and phosphorylated p38MAPK (p-p38MAPK) in human coronary artery endothelial cells (HCAECs) ex vivo. MethodsHCAECs were stressed with activated platelets (2×108/ml) and followed by ASP (1, 2 or 5mmol/l), EGb (4, 40 or 400μg/ml) and combinational (1mmol/l ASP and 40μg/ml EGb) treatments in three groups for 12h. Superoxide anion in HCAECs was measured with H2DCF-DA probe. The expressions of LOX-1 and p-p38MAPK were examined by Western blot. ResultsAfter stimulation of activated platelets, intracellular superoxide anion was increased about 3-folds in HCAECs. Both ASP and EGb reduced superoxide anion in HCAECs in a dosage dependent manner. Combinational administration of ASP and EGb showed synergistic effect. By Western blot analysis, we were able to show that activated platelets markedly enhanced the expressions of LOX-1 and p-p38MAPK. Both ASP and EGb only inhibited LOX-1 expression in a concentration-dependent manner, but not p-p38MAPK. As expected, the combination of ASP and EGb markedly reduced not only the expression of LOX-1 but also the phosphorylation of p38MAPK. ConclusionsBoth EGb and ASP attenuate the oxidative stress of HCAECs stimulated by activated platelets ex vivo. It appears that the synergistic effect of EGb and ASP may correlate with the inhibition of ROS production, LOX-1 expression and p38MAPK phosphorylation.