Crocin induces anti-ischemia in middle cerebral artery occlusion rats and inhibits autophagy by regulating the mammalian target of rapamycin

Abstract

Crocin, an active compound found in Gardenia jasminoides Ellis, has been shown to possess neuron-protective properties, but its potential mechanisms of action still remain poorly understood. In this study, the anti-ischemic effect and underlying mechanism of action of crocin were investigated in male rats with right middle cerebral artery occlusion/reperfusion. Computed tomography and magnetic resonance imaging were used to evaluate the area of infarction 24 h after reperfusion. Neurological scores were employed to evaluate nerve injury. Direct 2,3,5-triphenyltetrazolium chloride staining was used to calculate the infarct ratio 120 h after reperfusion. Finally, HT22 cells and Western blot were used to study the underlying mechanisms. Crocin showed a decreased infarct volume and neurological score in vivo, while the expression of LC3-II/I and AMP-activated protein kinase was remarkably down-regulated with increased levels of p62 and mammalian target of rapamycin (mTOR) expression. However, rapamycin significantly inhibited mTOR, which can impact the anti-ischemic effect of crocin in vitro. These results suggest that crocin may elicit an anti-ischemic effect probably through the mTOR pathway.

Keywords: Autophagy; Crocin; Mammalian target of rapamycin; Middle cerebral artery occlusion/reperfusion.