Mechanism of neuroprotective effect of stevioside on cerebral ischemia-reperfusion injury via PPAR-γ activation

The aim of this work was to explore the possible protective effects and its mechanism of stevioside on cerebral ischemia reperfusion (CIR) induced neuron damages.Middle cerebral artery occlusion/reperfusion (MCAO/R) rat models were constructed. The rats were treated with stevioside treatment, PPAR-γ antagonist GW9662, PPAR-γ activator pioglitazone or PI3K/AKT inhibitor LY294002 before neurological deficits were assessed using modified Neurological Severity Scale (mNSS) scores. The infarct size, brain injury, apoptotic cells, inflammatory cytokines in neurons extracted from MCAO/R rats were determined by TTC staining, H&E staining, TUNEL staining, qRT-PCR and Western blot, respectively.Stevioside attenuates MCAO/R-induced neuronal apoptosis and inflammation by regulating PPAR-γ expression. Besides, PPAR-γ activates PI3K/AKT signaling pathway. Moreover, PPAR-γ antagonist GW9662 or PI3K/AKT inhibitor LY294002 abrogated the anti-apoptosis and anti-inflammatory effects of stevioside on MCAO/R rats.Stevioside alleviates MCAO/R-induced neuronal apoptosis and inflammation by upregulating PPAR-γ to activate PI3K/AKT signaling pathway.