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 min, 24 h, and 48 h 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.