Icariin attenuates cerebral ischemia–reperfusion injury through inhibition of inflammatory response mediated by NF-κB, PPARα and PPARγ in rats

• Icariin has neuroprotective effect on ischemic stroke in rat.
• Icariin inhibits inflammatory responses in ischemic stroke.
• Icariin suppresses IκB degradation and NF-κB activation in ischemic stroke.
• Icariin up-regulates both PPARα and PPARγ protein levels in ischemic stroke.

Icariin (ICA), an active flavonoid extracted from Chinese medicinal herb Epimedii, has been reported to exhibit many pharmacological effects including alleviating brain injury. However, little is known about the protection of ICA on ischemic stroke. Hence, this study was designed to investigate the neuroprotective effect of ICA and explore its underlying mechanisms on ischemic stroke induced by cerebral ischemia–reperfusion (I/R) injury in rats. The animals were pretreated with ICA at doses of 10, 30 mg/kg twice per day for 3 consecutive days followed by cerebral I/R injury induced by middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 24 h. Neurological function and infarct volume were observed at 24 h after reperfusion, the protein expression levels of interleukin-1β (IL-1β), transforming growth factor-β1 (TGF-β1), PPARα and PPARγ, inhibitory κB-α (IκB-α) degradation and nuclear factor κB (NF-κB) p65 phosphorylation were detected by Western blot, respectively. It was found that pretreatment with ICA could decrease neurological deficit score, diminish the infarct volume, and reduce the protein levels of IL-1β and TGF-β1. Moreover, ICA suppressed IκB-α degradation and NF-κB activation induced by I/R. Furthermore, the present study also showed that ICA up-regulated PPARα and PPARγ protein levels. These findings suggest that ICA has neuroprotective effect on ischemic stroke in rats through inhibition of inflammatory responses mediated by NF-κB and PPARα and PPARγ.