6-shogaol alleviates excessive neuronal autophagy and calcium overload following cerebral ischemia-reperfusion injury by inhibiting the expression of DAPK1.

Abstract

Cerebral ischemia-reperfusion injury (CIRI) is the primary pathological mechanism of ischemic stroke, leading to neuronal damage and triggering a series of pathological changes. This study investigates the neuroprotective effects and underlying mechanisms of 6-shogaol (6-SH) in CIRI. By establishing an in vitro OGD/R model and a rat cerebral ischemia-reperfusion model, we found that 6-SH significantly improved neuronal viability, alleviated pathological damage, and reduced autophagosome formation. Additionally, 6-SH treatment markedly inhibited the expression of DAPK1, decreased intracellular calcium ion concentration, and mitigated excessive autophagy. Mechanistic studies indicated that 6-SH reduces neuronal injury induced by CIRI by modulating DAPK1 phosphorylation and inhibiting its activity. This discovery provides a theoretical basis for considering 6-SH as a potential neuroprotective agent and offers new insights for clinical treatment of ischemic stroke.