A Comprehensive Study On The Effects Of Ginkgo Biloba Extract On The Mechanism Of Atherosclerosis

Objective: To evaluate the effects of a single dose of Ginkgo biloba extract on the parameters of prothrombotic state(PTS).Methods: Database including MEDLINE, EMBASE, Cochrane Library, Chinese Biomedical Literature Database(CBM), China National Knowledge Infrastructure(CNKI) and Wanfang Data were searched from inception to May 7, 2015.Randomized controlled trials involving the healthy volunteers or patients receiving ginkgo biloba extract as compared with placebo were included. Parameters of the prothrombotic state including: platelet aggregation, activated partial thromboplastin time(APTT), prothrombin time(PT), plasma fibrinogen, blood viscosity, blood flow velocity. Risk of bias of allocation sequence, allocation concealment, blinding,incomplete outcome data, selective outcome reporting, and other biases were assessed by the Cochrane risk of bias assessment tool. The data was analyzed by the Cochrane collaboration’s Rev Man 5.0. The following statistical methods were used: weighted mean difference(WMD),standardized mean difference(SMD) and 95% confidence intervals(CIs). The results of the heterogeneity of the included studies were statistically homogeneous(P>0.1, I2<50%), the fixed effect model was used for Meta analysis;there is statistical heterogeneity such as the testing results(P<0.1, I2>50%), then find out the heterogeneous sources according to the sensitivity analysis, subgroup analysis or meta-regression analysis.Results: Fourteen RCTs from ten countries with 440 participants were analyzed.Ginkgo biloba extract group has significant improvements in the partial parameters of prothrombotic state as compared with placebo group. The result showed that Adenosine5’-diphosphate(ADP)-induced platelet aggregation was significantly inhibited [WMD-7.53%, 95%CI(-14.27,-0.78), P=0.03], the blood viscosity was significantly reduced[WMD-1.40 m Pa·s, 95%CI(-1.91,-0.89), P<0.00001], and the blood flow was increased [SMD 0.63, 95%CI(0.17, 1.09), P=0.008]. However, there were no significant differences observed between Ginkgo biloba extract and placebo treatments in APTT [WMD-0.25 s,95%CI(-0.68,0.19),P=0.26], PT [WMD-0.07 s,95%CI(-0.37,0.23), P=0.64], plasma fibrinogen [WMD-4.94mg/dl, 95%CI(-23.02, 13.15), P=0.59].Conclusions: Based on the result of Meta-analysis about the parameters of prothrombotic state, Ginkgo biloba extract may significantly reduce blood viscosity and also increase blood flow velocity as compared with placebo. Ginkgo biloba extract may significantly improve the partial parameters of prothrombotic state and inhibit the formation of thrombus.Background : Inflammation is a very important step in the pathogenesis of atherosclerosis. P38 MAPK signaling pathway plays an important role in the inflammatory reaction in endothelial cells. We postulated that therapeutic concentrations of aspirin and Ginkgo biloba extract(EGb), especially in combination, may inhibit activation of the P38 MAPK signal pathway in endothelial cells, and this concept was examined in human coronary artery endothelial cells(HCAECs).Methods: HCAECs were cultured and treated with activated platelets(2×108/ml)alone, or pre-treated with EGb(4, 40 or 400 μg/L), aspirin(1, 2 or 5 mmol/L) or their combination(40 μg/L EGb and 1 mmol/L aspirin), followed by activated platelets treatment in three groups for 1h. After respective treatment, Western blot were used to examine the expressions of p-MKK3/6, MKK3/6, p-p38 MAPK, p38 MAPK.Results: After induction of activated platelets, a synergistic effect was detected when administration combination of EGb and ASP. By Western blot analysis, it shows that activated platelets apparently enhanced the expressions of p-MKK3/6 and p-p38 MAPK. Both ASP and EGb, each acting alone, inhibited the expressions of p-MKK3/6 and p-p38 MAPK in a concentration-dependent manner. As expected, the combination of ASP and EGb markedly attenuated the phosphorylation of p38 MAPK and the phosphorylation of MKK3/6.Conclusions: Both EGb and ASP attenuate the inflammatory response of HCAECs induced by activated platelets. The synergistic effect of EGb and ASP may correlate with the expressions of p-MKK3/6 and p-p38 MAPK.