title: Astragaloside IV attenuates cognitive impairments induced by transient cerebral ischemia and reperfusion in mice via anti-inflammatory mechanisms.
abstract: Astragaloside IV (AS-IV) is the main active component isolated from the traditional Chinese medicinal herb Astragalus membranaceus. Studies have demonstrated that AS-IV has neuroprotective effects in cerebral ischemic models. In this study, we aimed to investigate the effects of AS-IV on memory impairment induced by transient cerebral ischemia and reperfusion in mice, as well as the associated signaling mechanisms. Severe memory deficits were induced by bilateral common carotid artery occlusion (BCCAO) in mice as indicated in the Morris water maze test in this study. Oral administration of AS-IV (10 and 20mg/kg, once per day, started 7days before surgery and continued for 7days after surgery) significantly attenuated memory impairment and neuroinflammation. Moreover, AS-IV treatment significantly reduced the expression of toll-like receptor-4 (TLR4) and its downstream adaptor proteins, including myeloid differentiation primary response gene 88 (MyD88), toll/interleukin-1 receptor-domain containing adaptor-inducing interferon-β (TRIF) and tumour necrosis factor receptor associated factor-6 (TRAF6), and subsequently inhibited NF-κB phosphorylation. It is well-known that cerebral ischemia and reperfusion injury enhances the formation of reactive oxygen species (ROS) and further neuroinflammation. Importantly, we found that AS-IV suppressed NLRP3 inflammasome activation by controlling ROS production. In addition, AS-IV markedly reduced overactivation of microglia and the overexpression of inflammatory cytokines in the hippocampus compared with the transient cerebral ischemia and reperfusion group. These results suggest that AS-IV might possess neuroprotective effects against transient cerebral ischemia and reperfusion partly through its anti-inflammatory effects by inhibiting TLR4 signaling pathway and NLRP3 inflammasome overactivation.
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Xueyang
authors.initials: X
authors.lastname: Deng
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; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D060825:Cognitive Dysfunction / Q000188:drug therapy*; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D015424:Reperfusion; D012503:Saponins / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D018696:Neuroprotective Agents; D012503:Saponins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014315:Triterpenes; C052064:astragaloside A
keywords: Astragaloside IV; Cerebral ischemia and reperfusion; Cognitive impairments; Microglial activation; NLRP3 inflammasome; TLR4 signaling pathway