title: Total bakkenolides protects neurons against cerebral ischemic injury through inhibition of nuclear factor-κB activation.
abstract: Total bakkenolides is the major component of the rhizome of Petasites trichinous Franch.. In this study, we investigated its neuroprotective effects in a rat transient focal cerebral ischemia-reperfusion model, and in an in vitro cerebral ischemia model, oxygen-glucose deprivation of cultured nerve cells. Oral administration of total bakkenolides immediately after reperfusion at doses of 5, 10 and 20 mg/kg markedly reduced brain infarct volume and neurological deficits. Total bakkenolides significantly attenuated cell death and apoptosis in primarily cultured neurons subject to 1-h hypoxia followed by 24-h reoxygenation. Morphologic observations directly confirmed its protective effect on neurons. We also demonstrated that total bakkenolides could inhibit nuclear factor-κB (NF-κB) activation by blocking the classic activation pathway through suppression of phosphorylation of IκB-kinase complex, NF-κB/p65 and inhibitor protein IκB, inducing nuclear translocation of NF-κB/p65 and degradation of IκB. Further, total bakkenolides inhibited the activation of Akt and the extracellular signal-regulated kinase 1/2, two important upstream activators of NF-κB. In conclusion, our results provide a strong pharmacological basis for further understanding the potential therapeutic role of total bakkenolides in cerebral ischemic disease and shed new light on its neuroprotective mechanism.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.forename: Yu-Ye
authors.initials: YY
authors.lastname: Xia
authors.forename: Jian-Ming
authors.initials: JM
authors.lastname: He
authors.forename: Mei-Li
authors.initials: ML
authors.lastname: Guo
authors.affiliation: (Mei-Li Guo) NO. 325, Guohe Road, Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China. mlguo@126.com.
authors.forename: Run-Ping
authors.initials: RP
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000150:complications / Q000517:prevention & control*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016328:NF-kappa B; D018696:Neuroprotective Agents; D012717:Sesquiterpenes