Huperzine A exhibits anti-inflammatory and neuroprotective effects in a rat model of transient focal cerebral ischemia.
Huperzine A, a reversible and selective acetylcholinesterase (AChE) inhibitor, has been reported to display neuroprotective properties. The present study investigated the protective effects of huperzine A in a rat model of transient focal cerebral ischemia created by middle cerebral artery occlusion (MCAO). Huperzine A (0.1 mg/kg), administrated intraperitoneally at the onset of occlusion and 6 h later, markedly restored regional cerebral blood flow, reduced infarct size, and decreased neurological deficit score at 24 h after reperfusion. Along with inhibiting AChE activity, huperzine A inhibited nuclear translocation of transcription factor nuclear factor-kappa B, decreased overexpression of proinflammatory factors in both ipsilateral cortex and striatum, and suppressed activation of glial cells in the ischemic penumbra. Neurological deficit and glial cells activation were also reduced by daily administration of huperzine A for 14 days. Mecamylamine, a nicotinic acetylcholine receptor (nAChR) antagonist, totally abolished the inhibitory effects of huperzine A on ischemia-induced glial cells activation. Meanwhile, mecamylamine partially reversed the infarct size-reducing effects of huperzine A. In conclusion, our results demonstrate that huperzine A exhibits neuroprotective effects against transient focal cerebral ischemia-induced brain injury and suggest that the protection mechanism may involve a cholinergic anti-inflammatory pathway, in which nAChR plays an essential role.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhangjiang Hi-Tech Park, Shanghai, P.R. China.
Zhi-Fei
ZF
Wang
Juan
J
Wang
Hai-Yan
HY
Zhang
Xi-Can
XC
Tang
D000470:Alkaloids; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004195:Disease Models, Animal; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000627:therapeutic use*
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018696:Neuroprotective Agents; D012717:Sesquiterpenes; C050426:huperzine A