Phellopterin Mitigates Cerebral Ischemia-Reperfusion Injury in Mice via NF-κB, COX-2 Inflammatory Pathway and OGD/R-Induced SH-SY5Y Cells

A stroke is a potentially fatal condition that occurs when there is a sudden blockage or blood vessel rupture in the brain, leading to a blockage in blood flow. Worldwide, ischemic brain damage relates to a high incidence of death and morbidity. The aim of the current work was to examine the neuroprotective properties of phellopterin against cerebral ischemic/reperfusion injury in a mouse model by assessing its anti-inflammatory and antioxidant capabilities. The experimental mice underwent the middle cerebral artery occlusion procedure to initiate ischemic/reperfusion injury. The experimental mice were then treated with phellopterin orally at different doses 2 h after the middle cerebral artery occlusion surgery. The infarct size, neurological deficit scores, and water content of the experimental mice were evaluated. The inflammatory cytokines, oxidative stress markers, and other biomarker levels were analyzed using commercially available kits. An immunohistochemical study was conducted to study the expression of inflammatory proteins. The neuroprotective properties of phellopterin were examined in brain tissues using histological techniques. Phellopterin treatment effectively alleviated the neurological impairments, water content, and infarct size in the middle cerebral artery occlusion-induced mice. Phellopterin treatment effectively reduced the levels of pro-inflammatory markers, increased the antioxidants, and regulated other biochemical markers. In addition, phellopterin has shown significant efficacy in reducing NF-kappa B and TLR4 expression levels. The phellopterin treatment successfully reduced brain histological changes in middle cerebral artery occlusion in mice. The current results could assist in the development of phellopterin as a therapeutic candidate to treat ischemic brain injury.