Zhongfeng capsule protects against cerebral ischemia-reperfusion injury via mediating PI3K/Akt and TLR4/NF-κB signal pathway regulated neuronal apoptosis and inflammatory reaction

Abstract

Inflammation reactions and neuronal apoptosis are the major pathophysiological mechanism of cerebral ischemia/reperfusion injury (CI/RI). Zhongfeng capsules (ZFCs), composed of panax notoginseng, hirudo, red ginseng, eupolyphaga, pangolin scales, rhubarb, and radix salviae miltiorrhizae. It has been reported that composition of ZFCs has a definite curative effect on CI/RI. Thus far, the specific molecular mechanisms of ZFCs remain unclear. This article would set rats model of middle cerebral artery occlusion(MCAO) to research the probable mechanisms of ZFCs underlying inflammation reactions and neuronal apoptosis signaling pathways. Our analyses revealed that in the ZFCs treatment group, there was an obvious decrease in neurologic impairment, as well as alleviation of the area of cerebral infarction, cerebral edema, histopathologyrats and neuronal apoptosis were also alleviated. The IL-1β, IL-6, and TNF-α were found to be down-regulated expression in the ZFC treatment group as well as the expression of Bcl-2, p-PI3K, p-Akt, and I-κBα was increased and the expression level of TLR4, NF-κB, Bax, caspase-3 was tended to decrease. The results indicated that ZFCs was effective in protecting the brain against CI/RI. One of their neuro-protective mechanisms may be associated with TLR4/NF-κB signalling, and they may negatively regulate the transcriptional activity of NF-κB and the secretion of downstream inflammatory factors. Another of their neuro-protective mechanisms may occur by regulating the expression of Bcl-2-Bax proteins of PI3K/Akt pathway. Our findings could facilitate that the suppressing PI3K/Akt signal pathway-mediated neuronal apoptosis, suppressing TLR4/NF-κB signal pathway-mediated inflammatory reaction were the potential mechanisms for the regulations, activation of PI3K/Akt pathway can inhibit the secretion of proinflammatory cytokines, which may be another functional mechanism of ZFCs against CI/RI.