Icariside II protects against cerebral ischemia-reperfusion injury in rats via nuclear factor-κB inhibition and peroxisome proliferator-activated receptor up-regulation

Icariside II (IRS) is a metabolite of icariin, which is derived from Herba Epimedii. Although the potential therapeutic effects of icariin on ischemic brain injury were well-investigated; the role of IRS in ischemic stroke is still not addressed clearly. Therefore, the current study aimed to evaluate the effects of IRS on cerebral ischemia-reperfusion injury in rats. The rats were pre-treated by IRS (10 or 30 mg kg(-1), twice a day) for 3 days. After pre-treatment, a MCAO (middle cerebral artery occlusion) for 2 h followed by reperfusion for 24 h was applied on the rats to induce the cerebral ischemia injury model. The neurological deficit scores were assessed at 24 h after reperfusion, then animals were sacrificed, infarct volumes were determined by 2,3,5-triphenyltetrazolium chlorid (TTC) staining and protein expression levels of interleukin-1 beta (IL-1 beta), transforming growth factor-beta(1) (TGF-beta(1)), inhibitory kappa B (I kappa B), nuclear factor kappa B (NF-kappa B) p65, peroxisome proliferator-activated receptor alpha (PPAR alpha), and peroxisome proliferator-activated receptor gamma (PPAR gamma) were assayed by using Western blot. IRS pretreatment markedly improved the neurological dysfunction and decreased infarct volume in MCAO rats. In addition, IRS inhibited IL-1 beta and TGF-beta(1) protein expression, and resulted in beneficial effects such as inhibition of I kappa B-alpha degradation and NF-kappa B activation induced by MCAO, in a dose-dependent manner. Furthermore, IRS increased the protein expression levels of PPAR alpha and PPAR gamma in the ischemic brain. In conclusion, pretreatment with IRS protects against cerebral ischemic/reperfusion injury via up-regulation of PPAR alpha and PPAR gamma and inhibition of NF-kappa B activation. (C) 2016 Elsevier Ltd. All rights reserved.