Biochanin A Provides Neuroprotection Against Cerebral Ischemia/Reperfusion Injury by Nrf2-Mediated Inhibition of Oxidative Stress and Inflammation Signaling Pathway in Rats

Background: Oxidative stress and neuroinflammation are 2 pivotal mechanisms in the progression of cerebral ischemia/reperfusion injury. Biochanin A, a natural phytoestrogen, has been reported to protect against ischemic brain injury in animal experiments, but the possible pharmacological mechanisms of its neuroprotection remain elusive. In this research, we sought to investigate the neuroprotective effects of biochanin A in experimental stroke rats and the probable mechanisms underlying oxidative stress and inflammation signaling pathways. Material/Methods: An ischemic stroke model was induced by inserting thread into the middle cerebral artery. Rats were pre-administered intraperitoneally with a vehicle solution or biochanin A (10, 20, or 40 mg.kg.d(-1)) for 14 days prior to ischemic stroke. Neurological score, infarct volume, and cerebral edema were assessed after 2 h of ischemia and 24 h of reperfusion. The activities of SOD and GSH-Px and MDA content were measured. The expressions of Nrf2, HO-1, and NE-kappa B and the activity of phosphor-I kappa B alpha were detected by Western blotting. Results: Biochanin A pretreatment significantly improved neurological deficit and decreased infarct size and brain edema. Biochanin A also enhanced SOD and GSH-Px activities and suppressed the production of MDA. Additionally, biochanin A promoted Nrf2 nuclear translocation, promoted the expression of HO-1, and inhibited NE-kappa B activation in ischemic brain injury. Conclusions: The results indicated that biochanin A protected the brain against ischemic injury in rats by anti-oxidative and anti-inflammatory actions. The activation of the Nrf2 pathway and the inhibition of the NE-kappa B pathway may contribute to the neuroprotective effects of biochanin A.