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.