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

• Published in: European journal of pharmacology Vol. 857; p. 172424
• Main Authors: Huang, Zhiheng, Xu, Jie, Huang, Xiaoyan, Sun, Guangda, Jiang, Ruizhi, Wu, Haoran, Shan, Xin, Bao, Ke, Wu, Qinan, Wu, Haoxin, Tao, Weiwei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.08.2019
• Subjects: Animals; Autophagy; Autophagy - drug effects; Carotenoids - pharmacology; Carotenoids - therapeutic use; Cell Survival - drug effects; Crocin; Down-Regulation - drug effects; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - pathology; Male; Mammalian target of rapamycin; Middle cerebral artery occlusion/reperfusion; Rats; Rats, Sprague-Dawley; TOR Serine-Threonine Kinases - metabolism; Middle cerebral artery occlusion/reperfusion; Autophagy; Crocin; Mammalian target of rapamycin
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2019.172424

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.