Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway

Puerarin,a major isoflavonoid derived from the Chinese medical herb radix puerariae(Gegen),has been reported to inhibit neuronal apoptosis and play an anti-inflammatory role in focal cerebra ischemia model rats.Recent findings regarding stroke pathophysiology have recognized that anti-inflammation is an important target for the treatment of ischemic stroke.The cholinergic anti-inflammatory pathway is a highly robust neural-immune mechanism for inflammation control This study was to investigate whether activating the cholinergic anti-inflammatory pathway can be involved in the mechanism of inhibiting the inflammatory response during puerarin-induced cerebra ischemia/reperfusion in rats.Results showed that puerarin pretreatment(intravenous injection)reduced the ischemic infarct volume,improved neurological deficit after cerebra ischemia/reperfusion and decreased the levels of interleukin-1β,interleukin-6 and tumor necrosis factor-αin brain tissue.Pretreatment with puerarin(intravenous injection)attenuated the inflammatory response in rats,which was accompanied by janus-activated kinase 2(JAK2)and signal transducers and activators of transcription 3(STAT3)activation and nuclear factor kappa B(NF-κB)inhibition.These observations were inhibited by the alpha7 nicotinic acetylcholine recepto(α7nAchR)antagonistα-bungarotoxin(α-BGT).In addition,puerarin pretreatment increased the expression ofα7nAchR mRNA in ischemic cerebral tissue.These data demonstrate that puerarin pretreatment strongly protects the brain against cerebral ischemia/reperfusion injury and inhibits the inflammatory response.Our results also indicated that the anti-inflammatory effect of puerarin may partly be mediated through the activation of the cholinergic anti-inflammatory pathway.