Equol is Neuroprotective During Focal Cerebral Ischemia and Reperfusion that Involves p-Src and gp91^phox

Title:Equol is Neuroprotective During Focal Cerebral Ischemia and Reperfusion that Involves p-Src and gp91^phox

Volume: 11 Issue: 4

Author(s): Wei Yu, Yan Wang, Dang-Xia Zhou, Li-Mei Zhao, Gui-Rong Li and Xiu-Ling Deng

Affiliation:

Keywords: Equol, focal cerebral ischemia/reperfusion, gp91^phox, neuroprotection, Src

Abstract: Both of gp91^phox (an isoform of nicotinamide adenine dinucleotide phosphate reduced oxidases) and Src (a nonreceptor protein tyrosine kinase) are abundantly expressed in the brain and play a prominent role in mediating ischemic alteration in neurons. The inhibitory strategy of them is believed to be the promising treatment of stroke. The present study was designed to investigate the effect of equol (0.625–2.5 mg·kg^-1, i.g. for 3 days), a predominant active metabolite of daidzein, on neuroprotection against cerebral ischemia/reperfusion injury in rats and the underlying mechanisms. We found that equol decreased the mortality, neurological deficit, brain histological damage, infarct volume, serum lactate dehydrogenase activity and malondialdehyde content in a dose-dependent manner in rats with 2-h middle cerebral artery occlusion, followed by 22-h reperfusion. Western blot analysis revealed that protein levels of gp91^phox and phosphorylated Src-Tyr416 (p-Src) in ischemic cerebral cortex were increased in rats treated with vehicle, which was reversed in animals treated with equol. In rat pheochromocytoma cell line (PC12) with hypoxia/reoxygenation injury, silencing of gp91^phox with specific siRNA did not affect the increase of p-Src level by hypoxia/reoxygenation injury and the inhibition of p-Src level by equol, while silencing of Src suppressed the upregulation of gp91^phox by hypoxia/reoxygenation injury and enhanced the inhibitory effect of equol on gp91^phox expression. These results demonstrate that equol confers a neuroprotection in rats via inhibiting the activation of Src and upregulation of gp91^phox induced by focal cerebral ischemia/reperfusion, and Src may play a partial role in regulating gp91^phox expression of neurons.

Cite this article as:

Yu Wei, Wang Yan, Zhou Dang-Xia, Zhao Li-Mei, Li Gui-Rong and Deng Xiu-Ling, Equol is Neuroprotective During Focal Cerebral Ischemia and Reperfusion that Involves p-Src and gp91^phox, Current Neurovascular Research 2014; 11 (4) . https://dx.doi.org/10.2174/1567202611666140908094517