Betulinic Acid Ameliorates Cerebral Injury in Middle Cerebral Artery Occlusion Rats through Regulating Autophagy

Abstract

Cerebral ischemic stroke (CIS) is an acute cerebrovascular disease that is caused by the sudden rupture of blood vessels inside the brain and the intervention of reperfusion to the brain, resulting in severe cerebral injury. Autophagy has been reported to be involved in the occurrence and progression of CIS. Betulinic acid (BA) is a pentacyclic triterpene acid mainly extracted from birch bark. Studies have shown the neuroprotective effects of BA. Here, the effect and mechanism of BA on ischemia-reperfusion induced cerebral injury was explored using a CIS model in vivo via 1 h middle cerebral artery occlusion (MCAO) and 24 h reperfusion in rats and in vitro via oxygen-glucose deprivation/reperfusion (OGD/R) of PC12 cells, respectively. We found that BA not only reduced cerebral injury by reducing oxidative stress but also activated the SIRT1/FoxO1 pathway to suppress autophagy and improve cerebral injury in MCAO rats. These results provide a basis for the potential clinical application of BA.