Gomisin A Attenuates Cerebral Ischemia/Reperfusion Injury Through Activation of the VEGF/PI3K/AKT/NOS3 Signaling...

Cerebral ischemia/reperfusion injury (CIRI) is a major cause of neurological dysfunction after ischemic stroke, and effective therapies remain limited. Gomisin A, a bioactive lignan isolated from Schisandra chinensis, exhibits antioxidant and anti-apoptotic activities, but its role in CIRI remains unclear. Here, the protective effects of Gomisin A were investigated using middle cerebral artery occlusion (MCAO) rats and oxygen-glucose deprivation/reoxygenation (OGD/R) cell models. Gomisin A significantly reduced cerebral infarct volume and improved neurological outcomes in MCAO rats. In OGD/R models, it enhanced endothelial cell migration and tube formation, accompanied by increased VEGF expression and activation of the VEGF/PI3K/AKT/NOS3 signaling pathway. In addition, Gomisin A alleviated oxidative stress and suppressed apoptosis in both cellular and animal models. Pharmacological inhibition of VEGF with axitinib partially reversed these protective effects, supporting the involvement of VEGF-dependent signaling. Collectively, these findings suggest that Gomisin A exerts neuroprotective effects against CIRI by enhancing angiogenic activity while attenuating oxidative stress and apoptosis, partly through activation of the VEGF/PI3K/AKT/NOS3 pathway. Gomisin A may therefore represent a promising candidate for the treatment of ischemic stroke.