title: Huperzine A attenuates mitochondrial dysfunction after middle cerebral artery occlusion in rats.
abstract: Mitochondrial dysfunction has been proved to contribute to ischemia-induced brain damage. In this study, which used a rat middle cerebral artery occlusion (MCAO) model, the protective effects of huperzine A (HupA) against mitochondrial dysfunction and brain damage were investigated. MCAO for 45 min followed by 4 hr of reperfusion significantly impaired the activities of mitochondrial respiratory chain enzymes (complex I, complex II-III, and complex IV) and alpha-ketoglutarate dehydrogenase, increased the production of reactive oxygen species (ROS), and induced mitochondrial swelling. Pretreatment of HupA at 0.1 mg/kg significantly preserved respiratory chain enzyme activities, decreased ROS production, and attenuated mitochondrial swelling. It could also significantly attenuate the neurological deficits (after 4 or 24 hr reperfusion) and reduce infarct volumes (after 24 hr reperfusion). Moreover, HupA protected isolated nonsynaptosomal mitochondria from calcium-induced damage in vitro by preserving mitochondrial membrane potential and decreasing ROS production. Overall, the present study indicates that HupA can ameliorate MCAO-induced mitochondrial dysfunction, and this might partially contribute to its protective effect on brain damage after 24 hr of reperfusion.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
authors.forename: Chun Yan
authors.initials: CY
authors.lastname: Zheng
authors.forename: Hai Yan
authors.initials: HY
authors.lastname: Zhang
authors.forename: Xi Can
authors.initials: XC
authors.lastname: Tang
mesh_terms: D000470:Alkaloids; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D033681:Mitochondrial Membrane Transport Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C050426:huperzine A