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

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 gamm...

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Main Authors: Lu Li, Guanghua Pan, Rong Fan, Dalei Li, Lei Guo, Lili Ma, Hui Liang, Jiaoxue Qiu
Format: Article
Language:English
Published: BMC 2022-07-01
Series:BMC Complementary Medicine and Therapies
Subjects:
Online Access:https://doi.org/10.1186/s12906-022-03652-8
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author Lu Li
Guanghua Pan
Rong Fan
Dalei Li
Lei Guo
Lili Ma
Hui Liang
Jiaoxue Qiu
author_facet Lu Li
Guanghua Pan
Rong Fan
Dalei Li
Lei Guo
Lili Ma
Hui Liang
Jiaoxue Qiu
author_sort Lu Li
collection DOAJ
description 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.
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spelling doaj.art-a0fbf12e557543888cf4426e59feb33e2022-12-22T01:20:48ZengBMCBMC Complementary Medicine and Therapies2662-76712022-07-0122111310.1186/s12906-022-03652-8Luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia/reperfusion by activating PPAR gamma in ratsLu Li0Guanghua Pan1Rong Fan2Dalei Li3Lei Guo4Lili Ma5Hui Liang6Jiaoxue Qiu7Department of Electrophysiology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong UniversityDepartment of Gastroenterology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong UniversityYantai Raphael Biotechnology Co.,LtdSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai UniversityDepartment of Neurology, Yantaishan HospitalDepartment of Neurology, Yantaishan HospitalDepartment of Neurology, Yantaishan HospitalDepartment of Neurology, Yantaishan HospitalAbstract 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.https://doi.org/10.1186/s12906-022-03652-8Cerebral ischemia-reperfusionPioglitazoneT0070907Molecular docking analysis
spellingShingle Lu Li
Guanghua Pan
Rong Fan
Dalei Li
Lei Guo
Lili Ma
Hui Liang
Jiaoxue Qiu
Luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia/reperfusion by activating PPAR gamma in rats
BMC Complementary Medicine and Therapies
Cerebral ischemia-reperfusion
Pioglitazone
T0070907
Molecular docking analysis
title Luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia/reperfusion by activating PPAR gamma in rats
title_full Luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia/reperfusion by activating PPAR gamma in rats
title_fullStr Luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia/reperfusion by activating PPAR gamma in rats
title_full_unstemmed Luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia/reperfusion by activating PPAR gamma in rats
title_short Luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia/reperfusion by activating PPAR gamma in rats
title_sort luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia reperfusion by activating ppar gamma in rats
topic Cerebral ischemia-reperfusion
Pioglitazone
T0070907
Molecular docking analysis
url https://doi.org/10.1186/s12906-022-03652-8
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