Salvianolic acid B inhibits hydrogen peroxide-induced endothelial cell apoptosis through regulating PI3K/Akt signaling

Background. Salvianolic acid B (Sal B) is one of the most bioactive components of Salvia miltiorrhiza, a traditional Chinese herbal medicine that has been commonly used for prevention and treatment of cerebrovascular disorders. However, the mechanism responsible for such protective effects remains largely unknown. It has been considered that cerebral endothelium apoptosis caused by reactive oxygen species including hydrogen peroxide (H₂O₂) is implicated in the pathogenesis of cerebrovascular disorders. Methodology and Principal Findings. By examining the effect of Sal B on H₂O₂-induced apoptosis in rat cerebral microvascular endothelial cells (rCMECs), we found that Sal B pretreatment significantly attenuated H₂O₂-induced apoptosis in rCMECs. We next examined the signaling cascade(s) involved in Sal B-mediated anti-apoptotic effects. We showed that H₂O₂ induces rCMECs apoptosis mainly through the PI3K/ERK pathway, since a PI3K inhibitor (LY294002) blocked ERK activation caused by H₂O₂ and a specific inhibitor of MEK (U0126) protected cells from apoptosis. On the other hand, blockage of the PI3K/Akt pathway abrogated the protective effect conferred by Sal B and potentated H₂O2_-induced apoptosis, suggesting that Sal B prevents H₂O₂-induced apoptosis predominantly through the PI3K/Akt (upstream of ERK) pathway. Significance. Our findings provide the first evidence that H₂ O₂ induces rCMECs apoptosis via the PI3K/MEK/ERK pathway and that Sal B protects rCMECs against H₂O₂-induced apoptosis through the PI3K/Akt/Raf/MEK/ERK pathway.