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

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.

Implantable Epigallocatechin Gallate Sustained-Release Nanofibers for the Prevention of Immobilization-Induced Muscle Atrophy

“…EGCG itself could produce hypoxic protection and promote cell differentiation by regulating Akt signaling. 37,38 In this study, EPLA promoted the phosphorylation of S473 of Akt and T28 of FoxO4. Combined with the results of previous studies, we speculated that EPLA could inhibit the nuclear entry of Foxo4 transcription factor by promoting the phosphorylation of Akt S473, thereby inhibiting the production of atrophin (Figure 6).…”

A bibliometric analysis of research foci and trends in cerebral ischemia-reperfusion injury involving autophagy during 2008 to 2022

“…Additionally, (-)-Epigallocatechin-3-gallate (EGCG), a bioactive component found in green tea, can inhibit autophagy via the AKT/AMPK/mTOR phosphorylation pathway, thus preventing further reperfusion injury in the mouse brain. [59]…”

Neuroprotective agents in acute ischemic stroke

“…In a study involving adult rats, after inducing middle cerebral artery occlusion injury, it was shown that EGCG exerted a neuroprotective effect by regulating caspase-3 and poly(adenosine diphosphate-ribose) polymerases (PARP) proteins during cerebral ischemia [94]. Another animal study confirmed that EGCG inhibited autophagy by modulating the protein kinase B (AKT)/5'adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) phosphorylation pathway in both in vivo and in vitro models of stroke [95].…”