title: Ruscogenin reduces cerebral ischemic injury via NF-κB-mediated inflammatory pathway in the mouse model of experimental stroke.
abstract: Transient cerebral ischemia initiates a complex series of inflammatory events, which has been associated with an increase in behavioral deficits and secondary brain damage. Ruscogenin is a major steroid sapogenin in the traditional Chinese herb Ophiopogon japonicus that have multiple bioactivities. Recent studies have demonstrated that Ruscogenin is involved in down-regulation of intercellular adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) activation in anti-inflammatory pathways. We hypothesized that Ruscogenin protects against brain ischemia by inhibiting NF-κB-mediated inflammatory pathway. To test this hypothesis, adult male mice (C57BL/6 strain) were pretreated with Ruscogenin and then subjected to transient middle cerebral artery occlusion (MCAO)/reperfusion. After 1 h MCAO and 24 h reperfusion, neurological deficit, infarct sizes, and brain water content were measured. Ruscogenin markedly decreased the infarct size, improved neurological deficits and reduced brain water content after MCAO. The activation of NF-κB Signaling pathway was observed after 1h of ischemia and 1h of reperfusion, and Ruscogenin significantly inhibited NF-κB p65 expression, phosphorylation and translocation from cytosol to nucleus at this time point in a dose-dependent manner. NF-κB DNA binding activity, and the expression of NF-κB target genes, including ICAM-1, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were also suppressed by Ruscogenin pretreatment after 1 h MCAO and 24 h reperfusion. The results indicated that Ruscogenin protected the brain against ischemic damage caused by MCAO, and this effect may be through downregulation of NF-κB-mediated inflammatory responses.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, PR China.
authors.forename: Teng
authors.initials: T
authors.lastname: Guan
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Yisong
authors.initials: Y
authors.lastname: Qian
authors.forename: Haopeng
authors.initials: H
authors.lastname: Yang
authors.forename: Jiming
authors.initials: J
authors.lastname: Kong
authors.forename: Junping
authors.initials: J
authors.lastname: Kou
authors.forename: Boyang
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D013150:Spirostans / Q000494:pharmacology* / Q000627:therapeutic use; D020521:Stroke / Q000150:complications*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D018696:Neuroprotective Agents; D013150:Spirostans; C012541:ruscogenin
keywords: Inflammation; Middle cerebral artery occlusion; NF-κB; Ruscogenin; Stroke