α-Cyperone safeguards against cerebral ischaemia‒reperfusion injury through the activation of the Nrf2 signalling pathway.

Neuroinflammation is a significant factor that exacerbates secondary damage following cerebral ischaemia/reperfusion (CI/R) injury. α-Cyperone (CYP), the principal active constituent of the traditional Chinese medicine Cyperus rotundus L., decreases inflammation. Nonetheless, its impact on CI/R injury remains unknown. Here, we examined the potential involvement of CYP in regulating CI/R injury-induced oxidative stress and apoptosis. Middle cerebral artery occlusion was used to establish a model of CI/R injury in male C57BL/6J mice. CYP (5 or 10 mg/kg) was administered by intraperitoneal injection 30 minutes, 24 hours, and 48 hours after model establishment. CYP markedly diminished the lesion volume, enhanced neuronal function and reduced apoptosis and oxidative stress. Moreover, CYP increased Nrf2, HO-1, NQO1, and SOD-1 expression in vivo, protecting neurons against hemin stimulation by facilitating Nrf2 nuclear translocation. ML385 (an Nrf2 inhibitor) fully abolished the protective effects of CYP in vivo following CI/R injury. Our data indicate that CYP mitigates CI/R injury-induced apoptosis and oxidative stress through Nrf2 signalling pathway activation, suggesting the possible therapeutic effect of CYP on CI/R injury.