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

BMC Complement Med Ther. 2022 Jul 1;22(1):176. doi: 10.1186/s12906-022-03652-8.

Abstract

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.

Keywords: Cerebral ischemia-reperfusion; Molecular docking analysis; Pioglitazone; T0070907.

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Brain Ischemia* / drug therapy
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Inflammation / drug therapy
  • Luteolin* / pharmacology
  • Molecular Docking Simulation
  • PPAR gamma / metabolism
  • Pioglitazone / pharmacology
  • Rats
  • Reperfusion
  • Reperfusion Injury* / drug therapy

Substances

  • PPAR gamma
  • Luteolin
  • Pioglitazone