Objective:To elucidate the underlying mechanism of Panax notoginseng saponin(PNS)on gastric epithelial cell injury and barrier dysfunction induced by dual antiplatelet(DA).Methods:Human gastric mucosal epithelial cell(GES-1)was cultured and divided into 4 groups:a control,a DA,a PNS+DA and a LY294002+PNS+DA group.GES-1 apoptosis was detected by flow cytometry,cell permeability were detected using Transwell,level of prostaglandins E2(PGE2),6-keto-prostaglandin F1α(6-keto-PGF1α)and vascular endothelial growth factor(VEGF)in supernatant were measured by enzyme linked immunosorbent assay(ELISA),expression of phosphatidylinositide 3-kinase(PI3K),phosphorylated-PI3K(p-PI3K),Akt,phosphorylated-Akt(p-Akt),cyclooxygenase-1(COX-1),cyclooxygenase-2(COX-2),glycogen synthase kinase-3β(GSK-3β)and Ras homolog gene family member A(RhoA)were measured by Western-blot.Results:DA induced apoptosis and hyper-permeability in GES-1,reduced supernatant level of PGE2,6-keto-PGF1α and VEGF(P＜0.05).Addition of PNS reduced the apoptosis of GES-1 caused by DA,restored the concentration of PGE2,6-keto-PGF1αand VEGF(P＜0.05).In addition,PNS attenuated the alteration of COX-1 and COX-2 expression induced by DA,up-regulated p-PI3K/p-Akt,down-regulated RhoA and GSK-3β.LY294002 mitigated the effects of PNS on cell apoptosis,cell permeability,VEGF concentration,and expression of RhoA and GSK-3β significantly.Conclusions:PNS attenuates the suppression on COX/PG pathway from DA,alleviates DA-induced GES-1 apoptosis and barrier dysfunction through PI3K/Akt/VEGF-GSK-3β-RhoA network pathway.