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26 November 2019 : Animal Research  

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

Minmin Guo1BCDEF, Huiling Lu12BCDEF, Jian Qin3CEFG, Shengbiao Qu1BCDEF, Wenbo Wang4CDEF, Yanhong Guo5BCEF, Weiyong Liao5CDF, Mengwei Song6BDF, Jian Chen1ACDEFG*, Yong Wang15ABCDEFG

DOI: 10.12659/MSM.918665

Med Sci Monit 2019; 25:8975-8983

Abstract

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 AND 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 NF-κB and the activity of phosphor-IκBα 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 NF-κB 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 NF-κB pathway may contribute to the neuroprotective effects of biochanin A.

Keywords: NF-E2-Related Factor 2, Phytoestrogens, Stroke, Brain, Brain Edema, Brain Ischemia, Gene Expression Regulation, Genistein, Infarction, Middle Cerebral Artery, neuroprotection, Neuroprotective Agents, Reperfusion Injury

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750