Huperzine A exhibits anti-inflammatory and neuroprotective effects in a rat model of transient focal cerebral ischemia.

Abstract

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.

• Authors: Zhi-Fei Wang, Juan Wang, Hai-Yan Zhang, Xi-Can Tang
• Journal: Journal of neurochemistry (J Neurochem) Vol. 106 Issue 4 Pg. 1594-603 (Aug 2008) ISSN: 1471-4159 [Electronic] England
• PMID: 18513368 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Anti-Inflammatory Agents, Non-Steroidal
• Neuroprotective Agents
• Sesquiterpenes
• huperzine A

Topics

• Alkaloids
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Disease Models, Animal
• Ischemic Attack, Transient (drug therapy, pathology, prevention & control)
• Male
• Neuroprotective Agents (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Sesquiterpenes (therapeutic use)