Saponins from Aralia taibaiensis protect against brain ischaemia/reperfusion injuries by regulating the apelin/AMPK pathway

Aralia taibaiensis, a species of Aralia, is widely distributed in western China, especially in the Qinba Moubtains, has been used as folk medicine for the treatment of diabetes, gastropathy, rheumatism, and cardiovascular diseases. Saponins from Aralia taibaiensis (sAT) have been shown to possess protective effects against oxidative stress and mitochondrial dysfunction induced by ischemia/reperfusion (I/R). However, the underling mechanisms are still unknown. In vivo, MCAO/R induced inflammatory infiltration, neuronal injury, cell apoptosis, mitochondrial dysfunction, and oxidative stress in the ischaemic penumbra, which can be effectively alleviated by sAT. sAT induces the mRNA and protein expression levels of apelin and its receptor AR both in vivo and in vitro. The regulatory effects of sAT on neuroprotective mediated by AMPK/akt were abolished by the AR antagonist F13A and siRNA. Furthermore, we found that sAT induced apelin/AR expression by simultaneously inhibiting P38 MAPK/ATF4 and upregulating HIF-1a. Our data demonstrated that sAT regulated apelin/AR/AMPK by inhibiting P38 MAPK/ATF4 and upregulating HIF-1a, thereby inhibiting oxidative stress and mitochondrial dysfunction.