title: Chrysophanol inhibits NALP3 inflammasome activation and ameliorates cerebral ischemia/reperfusion in mice.
abstract: The most effective way to contain cerebral ischemic injury is reperfusion; however, reperfusion itself may result in tissue injury, for which inflammatory damage is one of the main causative factors. NALP3 inflammasome is a multiprotein complex. It consists of NALP3, ASC, and caspase-1, whose function is to switch on the inflammatory process. Chrysophanol is an extract from plants of Rheum genus and it possesses many pharmacological effects including its anti-inflammation activity. In this study, the effects of chrysophanol in cerebral ischemia/reperfusion and the potential mechanisms were investigated. Male CD1 mice were subject to transient middle cerebral artery occlusion (tMCAO). The NALP3 inflammasome activation status and its dynamic expression during the natural inflammatory response induced by tMCAO were first profiled. The neuroprotective effects of chrysophanol were then assessed and the potential mechanisms mediating the observed neuroprotection were then explored. Physical parameters including neurological deficit, infarct size, brain edema, and BBB permeability were measured at 24 h after tMCAO. Confocal microscopy, Western blotting, immunohistochemistry, and qRT-PCR techniques were utilized to analyze the expression of NALP3 inflammasome and IL-1 β . Our results indicated that the brain tissue damage during cerebral ischemia/reperfusion is accompanied by NALP3 inflammasome activation. Chrysophanol could inhibit the activation of NALP3 inflammasome and protect cerebral ischemic stroke.
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China ; Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Shijiazhuang, Hebei 050000, China ; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, China.
authors.forename: Xiangjian
authors.identifier: 0000-0003-0114-1668
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Kang
authors.affiliation: Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Shijiazhuang, Hebei 050000, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D002544:Cerebral Infarction / Q000473:pathology; D004195:Disease Models, Animal; D058847:Inflammasomes / Q000187:drug effects*; D007249:Inflammation; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010539:Permeability; D010936:Plant Extracts / Q000494:pharmacology; D015427:Reperfusion Injury / Q000378:metabolism*; D020521:Stroke / Q000517:prevention & control
chemical_list: D000880:Anthraquinones; D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D010936:Plant Extracts; C027113:chrysophanic acid