title: Umbelliferone ameliorates cerebral ischemia-reperfusion injury via upregulating the PPAR gamma expression and suppressing TXNIP/NLRP3 inflammasome.
abstract: Umbelliferone (UMB), a natural antioxidant belonging to coumarin derivatives, is able to cross the blood-brain barrier and protect neuronal cells from death. Here we aimed to investigate the effects of UMB in a rat model of focal cerebral ischemia induced by middle cerebral artery occlusion/reperfusion (MCAO/R). Pretreatment with UMB (15 and 30 mg/kg) for 7 consecutive days ameliorated the neurological outcomes, infarct volume and brain edema in brains of MCAO rats. Our results provided evidence that UMB significantly protected neuronal cells against cerebral ischemia reperfusion-induced injury. Furthermore, UMB treatment could inhibited the level of oxidative stress and the production of inflammatory cytokines in brain tissues of MCAO rats. In addition, UMB significantly upregulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), which exhibited neuroprotective effects in neurodegenerative disease. UMB treatment also suppressed NLRP3 inflammasome activation via reducing expression of Thiredoxin-interactive protein (TXNIP). These results suggest that UMB may have beneficial effects for neuroprotection against focal cerebral ischemic partly through the inhibition of TXNIP/NLRP3 inflammasome and activation of PPAR-γ.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Xiangxiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Ruipeng
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: spma@cpu.edu.cn.
authors.forename: Shiping
authors.initials: S
authors.lastname: Ma
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D001929:Brain Edema / Q000188:drug therapy; D020520:Brain Infarction / Q000188:drug therapy / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D018797:Cell Cycle Proteins; D005786:Gene Expression Regulation; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D047495:PPAR gamma / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D014468:Umbelliferones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D018696:Neuroprotective Agents; C573346:Nlrp3 protein, rat; D047495:PPAR gamma; C493796:TXNIP protein, rat; D014468:Umbelliferones; D008315:Malondialdehyde; C031477:7-hydroxycoumarin; D013482:Superoxide Dismutase
keywords: Cerebral ischemia–reperfusion; NLRP3 inflammasome; PPAR-γ; TXNIP; Umbelliferone