Luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia/reperfusion by activating PPAR gamma in rats

Background: Luteolin, a flavonoid compound with anti-inflammatory activity, has been reported to alleviate cerebral ischemia/reperfusion (I/R) injury. However, its potential mechanism remains unclear.

Methods: The binding activity of luteolin to Peroxisome Proliferator-activated Receptor gamma (PPARγ) was calculated via molecular docking analysis. Rats were subjected to middle cerebral artery occlusion and reperfusion (MCAO/R). After reperfusion, vehicle, 25 mg/kg/d luteolin, 50 mg/kg/d luteolin, 10 mg/kg/d pioglitazone, 50 mg/kg/d luteolin combined with 10 mg/kg/d T0070907 (PPARγ Inhibitor) were immediately orally treatment for 7 days. ELISA, TTC staining, H&E staining, immunohistochemistry, immunofluorescence and transmission electron microscope methods were performed to evaluate the inflammation and Autophagy in damaged hippocampal region. The PPARγ, LIGHT chain 3 (LC3) B-II/LC3B-I and p-nuclear factor-κB (NF-κB) p65 proteins expression levels in damaged hippocampal region were analyzed.

Results: Luteolin showed good PPARγ activity according to docking score (score = - 8.2). Luteolin treatment downregulated the infarct area and the pro-inflammatory cytokines levels caused by MCAO/R injury. Moreover, luteolin administration ameliorated neuroinflammation and Autophagy in damaged hippocampal region. Pioglitazone plays protective roles similar to luteolin. T0070907 concealed the neuroprotective roles of 50 mg/kg/d luteolin.

Conclusions: Luteolin exerts neuroprotective roles against inflammation and Autophagy of hippocampus induced by cerebral I/R by activating PPARγ in rats.