EGCG protects the mouse brain against cerebral ischemia/reperfusion injury by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway

Li Wang; Maosha Dai; Yangyang Ge; Jiayi Chen; Chenchen Wang; Chengye Yao; Yun Lin

doi:10.3389/fphar.2022.921394

EGCG protects the mouse brain against cerebral ischemia/reperfusion injury by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway

Front Pharmacol. 2022 Sep 6:13:921394. doi: 10.3389/fphar.2022.921394. eCollection 2022.

Authors

Li Wang¹, Maosha Dai¹, Yangyang Ge¹, Jiayi Chen¹, Chenchen Wang¹, Chengye Yao², Yun Lin¹

Affiliations

¹ Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

Stroke remains one of the leading reasons of mortality and physical disability worldwide. The treatment of cerebral ischemic stroke faces challenges, partly due to a lack of effective treatments. In this study, we demonstrated that autophagy was stimulated by transient middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R). Treatment with (-)-epigallocatechin-3-gallate (EGCG), a bioactive ingredient in green tea, was able to mitigate cerebral ischemia/reperfusion injury (CIRI), given the evidence that EGCG administration could reduce the infarct volume and protect poststroke neuronal loss in MCAO/R mice in vivo and attenuate cell loss in OGD/R-challenged HT22 cells in vitro through suppressing autophagy activity. Mechanistically, EGCG inhibited autophagy via modulating the AKT/AMPK/mTOR phosphorylation pathway both in vivo and in vitro models of stroke, which was further confirmed by the results that the administration of GSK690693, an AKT/AMPK inhibitor, and rapamycin, an inhibitor of mTOR, reversed aforementioned changes in autophagy and AKT/AMPK/mTOR signaling pathway. Overall, the application of EGCG relieved CIRI by suppressing autophagy via the AKT/AMPK/mTOR phosphorylation pathway.

Keywords: (−)-epigallocatechin-3-gallate (EGCG); AKT/AMPK/mTOR pathway; HT22 cell; autophagy; cerebral ischemia/reperfusion injury (CIRI); middle cerebral artery occlusion/reperfusion (MCAO/R); oxygen-glucose deprivation/reoxygenation (OGD/R).