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

Abstract 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-1β (IL-1β), transforming growth factor-β 1 (TGF-β 1 ), inhibitory κB (IκB), nuclear factor κB (NF-κB) p65, peroxisome proliferator-activated receptor α (PPARα), and peroxisome proliferator-activated receptor γ (PPARγ) 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-1β and TGF-β 1 protein expression, and resulted in beneficial effects such as inhibition of IκB-α degradation and NF-κB activation induced by MCAO, in a dose-dependent manner. Furthermore, IRS increased the protein expression levels of PPARα and PPARγ in the ischemic brain. In conclusion, pretreatment with IRS protects against cerebral ischemic/reperfusion injury via up-regulation of PPARα and PPARγ and inhibition of NF-κB activation.