Icariin (ICA) has neuroprotection in oxygen-glucose deprivation (OGD) neurons by increasing Sirtuin1 (SIRT1). However, little is known about the role of ICA on stroke. SIRT1 is a class III histone deacetylase and activates peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) which stimulates mitochondrial activity. This study aims to investigate the expression of SIRT1 and PGC-1alpha during ICA's neuroprotection against ischemia. In vivo, behavioral test, infarct size and brain water content were evaluated on middle cerebral artery occlusion (MCAO) mouse models treated by ICA/saline. In vitro, primary cortical neurons were tortured by OGD in the presence of ICA or SIRT1 inhibitor III or PGC-1alpha siRNA. Cell viability and mortality were measured by MTT and flow cytometer assay. Knockdown efficiency of PGC-1alpha siRNA was measured by real time PCR. Expressions of SIRT1 and PGC-1alpha were also investigated. In result, neurological scores, infarct size and brain edema were all significantly improved, the cortical expressions of SIRT1 and PGC-1alpha were higher with ICA compared to the control (P < 0.05), and reversed by SIRT1 inhibitor III/PGC-1alpha siRNA. In conclusion, ICA protects against brain ischemic injury by increasing the SIRT1 and PGC-1alpha expression, potentially to be a neuroprotectant for ischemic brain injury.
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