Betulinic acid protects against cerebral ischemia/reperfusion injury by activating the PI3K/Akt signaling pathway.

Betulinic acid (BA), a naturally occurring pentacyclic lupane group triterpenoid, has been demonstrated to protect against ischemia/reperfusion-induced renal damage. However, the effects of BA on cerebral ischemia/reperfusion (I/R) injury remain unclear. Hence, this study was to investigate the effects of BA on oxygen and glucose deprivation/reperfusion (OGD/R) induced neuronal injury in rat hippocampal neurons. Our results showed that BA pretreatment greatly attenuated OGD/R-induced neuronal injury. BA also inhibited OGD/R-induced intracellular ROS production and MDA level in rat hippocampal neurons. Furthermore, the down-regulation of Bcl-2, up-regulation of Bax and the consequent activation of caspase-3 induced by OGD/R were reversed by BA pretreatment. Mechanistic studies demonstrated that BA pretreatment up-regulated the expression levels of p-PI3K and p-Akt in hippocampal neurons induced by OGD/R. Taken together, these data suggested that BA inhibits OGD/R-induced neuronal injury in rat hippocampal neurons through the activation of PI3K/Akt signaling pathway.