Abstract
Microglial over-activation and apoptosis are associated with ischemic brain diseases. These processes may be hindered by oxysophocarpine (OSC) that generates anti-inflammatory and anti-apoptotic activities. However, the precise roles of OSC in microglial inflammation and apoptosis induced by oxygen-glucose deprivation/reoxygenation (OGD/R) remain unclear. In this study, we found that OSC reduced OGD/R-induced inflammation in BV-2 microglia. OSC elevated cell viability and prevented the release of lactate dehydrogenase. OSC downregulated cyclooxygenase 2 and inducible nitric oxide synthase and reduced the levels of inflammatory mediators, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein-1, prostaglandin E2, and nitric oxide. OSC inhibited the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation protein 88 (MyD88) and blocked the activation of nuclear factor (NF)-κB. In addition, OSC suppressed OGD/R-elicited BV-2 cell apoptosis, as indicated as follows: The restored mitochondrial membrane potential and the reduced caspase-3 activity; the decrease of Bax and cleaved caspase-3 and the increase of Bcl-2; the enhanced phosphorylation of Akt and mTOR. These results implied that OSC impedes OGD/R-induced inflammation and apoptosis of microglial cells. Therefore, OSC may be potentially used for ischemic stroke therapy.