Icariin protects against brain injury by enhancing SIRT1-dependent PGC-1α Expression in experimental stroke

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-1α (PGC-1α) which stimulates mitochondrial activity. This study aims to investigate the expression of SIRT1 and PGC-1α 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-1α siRNA. Cell viability and mortality were measured by MTT and flow cytometer assay. Knockdown efficiency of PGC-1α siRNA was measured by real time PCR. Expressions of SIRT1 and PGC-1α were also investigated. In result, neurological scores, infarct size and brain edema were all significantly improved, the cortical expressions of SIRT1 and PGC-1α were higher with ICA compared to the control (P < 0.05), and reversed by SIRT1 inhibitor III/PGC-1α siRNA. In conclusion, ICA protects against brain ischemic injury by increasing the SIRT1 and PGC-1α expression, potentially to be a neuroprotectant for ischemic brain injury.