title: Biochanin A protects against focal cerebral ischemia/reperfusion in rats via inhibition of p38-mediated inflammatory responses.
abstract: Biochanin A, an O-methylated natural isoflavonoid classified as phytoestrogen, has been reported to show anti-tumorigenesis, anti-oxidation, and anti-inflammatory properties. However, little is known about the effects of biochanin A on cerebral ischemia/reperfusion. In this study, the neuroprotective and anti-inflammatory effects of biochanin A against ischemia/reperfusion injury, as well as the related molecular mechanisms, were investigated in rat models. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 2h, followed by 24h of reperfusion. Then neurological deficits, infarct volume and brain edema were evaluated. The MPO activity and TNF-α and IL-1β levels in ischemic boundary zone were determined by a spectrophotometer and the enzyme-linked immunosorbent assay (ELISA). The expressions of TNF-α, IL-1β, and phosphorylation of p38 were measured by RT-PCR or Western blotting. Consequently, our findings showed that biochanin A treatment for 14 days had significantly reduced infarct volume and brain edema, and improved neurological deficits in focal cerebral ischemia/reperfusion rats. The MPO activity and TNF-α and IL-1β levels were greatly increased after ischemia/reperfusion injury, while treatment with biochanin A dramatically suppressed these inflammatory processes. Furthermore, biochanin A attenuated the increase in p-p38 level in the ischemia/reperfusion brain tissue. Taken together, biochanin A has been shown to have neuroprotective effects in cerebral ischemia/reperfusion, and the mechanisms may correlate with inhibiting inflammatory response, as well as the inactivation of p38 signaling pathway.
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, China.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, China.
authors.forename: Lejian
authors.initials: L
authors.lastname: Tang
authors.affiliation: Guilin Medical University, Guilin 541004, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Physiology, Guilin Medical University, Guilin 541004, China. Electronic address: guilinchenjian@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications*; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D048789:Phytoestrogens / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*
chemical_list: D018696:Neuroprotective Agents; D048789:Phytoestrogens; D019833:Genistein; C004541:biochanin A
keywords: Biochanin A; Cerebral ischemia/reperfusion; Inflammation; MPO; TNF-α; p38