Huperzine A attenuates mitochondrial dysfunction after middle cerebral artery occlusion in rats.
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.
Zheng
Chun Yan
CY
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Zhang
Hai Yan
HY
Tang
Xi Can
XC
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*
D000470:Alkaloids; D033681:Mitochondrial Membrane Transport Proteins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C050426:huperzine A