title: Puerarin partly counteracts the inflammatory response after cerebral ischemia/reperfusion via activating the cholinergic anti-inflammatory pathway.
abstract: 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 cerebral 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 cerebral ischemia/reperfusion in rats. Results showed that puerarin pretreatment (intravenous injection) reduced the ischemic infarct volume, improved neurological deficit after cerebral ischemia/reperfusion and decreased the levels of interleukin-1β, interleukin-6 and tumor necrosis factor-α in 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 receptor (α7nAchR) antagonist α-bungarotoxin (α-BGT). In addition, puerarin pretreatment increased the expression of α7nAchR 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.
authors.affiliation: Medical College of China Three Gorges University, Yichang 443002, Hubei Province, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Liu
authors.affiliation: Medical College of China Three Gorges University, Yichang 443002, Hubei Province, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Mei
authors.affiliation: Medical College of China Three Gorges University, Yichang 443002, Hubei Province, China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Qian
authors.affiliation: Medical College of China Three Gorges University, Yichang 443002, Hubei Province, China.
authors.forename: Yongbao
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Medical College of China Three Gorges University, Yichang 443002, Hubei Province, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Wang
keywords: alpha7 nicotinic acetylcholine receptors; cerebral ischemia/reperfusion; cholinergic anti-inflammatory pathway; grants-supported paper; inflammation; janus-activated kinase 2; neural regeneration; neuroregeneration; nuclear factor kappa B; signal transducers and activators of transcription 3