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

Abstract

BackgroundOxidative 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/MethodsAn 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 NF-κB and the activity of phosphor-IκBα were detected by Western blotting.ResultsBiochanin 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 NF-κB activation in ischemic brain injury.ConclusionsThe 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 NF-κB pathway may contribute to the neuroprotective effects of biochanin A.

From Preclinical Stroke Models to Humans: Polyphenols in the Prevention and Treatment of Stroke

“…Biochanin A, a natural isoflavonoid phytoestrogen derived from red clover or chickpea, displays a broad range of pharmacological functions, including neuroprotective activities [ 202 ]. The molecule was effective in alleviating brain damage and symptoms of rodents subjected to tMCAO [ 203 , 204 ] and SAH [ 205 ]. The activation of the protective factors glutamate oxaloacetate transaminase (GOT), SOD and Nrf2 and the inhibition of the NF-kB pathway may contribute to the neuroprotective effects of biochanin A [ 203 , 204 , 205 ].…”

S100a8 silencing attenuates inflammation, oxidative stress and apoptosis in BV2 cells induced by oxygen‑glucose deprivation and reoxygenation by upregulating GAB1 expression

“…The excessive production of reactive oxygen species (ROS) results in the imbalance of oxidation and antioxidants in organisms, which plays a catalytic role in the progression of cerebral I/R injury ( 33 ). MDA, the end product of lipid peroxidation induced by ROS during oxidative stress, causes oxidative damage by destroying multiple biomacromolecules in biological membranes or organelles, such as lipids, enzymes and nucleic acids ( 34 , 35 ). In addition, SOD and GSH-Px, important antioxidant enzymes, can suppress and attenuate brain tissue injury induced by ROS cytotoxicity during I/R ( 36 ).…”

Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling Mechanisms

“…The phytoestrogen Genistein exhibited neuroprotective effects following ischemic stroke in rats by targeting NF-κB signaling and possibly by inhibiting downstream inflammatory immune cells in the brain [ 31 ]. Similarly, the phytoestrogen biochanin A provided neuroprotection against cerebral ischemia-reperfusion injury by Nrf2-mediated inhibition of oxidative stress and inflammation signaling pathway in rats [ 32 ]. All in all, these results indicate that genistein, biochanin A, and daidzein could have a therapeutic potential in neuroprotection and neurorepair.…”