Huperzine A (HupA),a novel alkaloid isolated flom the Chinese herb Huperziaserrata,is a potent,highly specific and reversible inhibitor of acetylcholinesterase(ACHE).Compared with tacrine,donepezil,and rivastigmine,HupA has betterpenetration through the blood-brain barrier,higher oral bioavailability,and longerduration of AChE inhibitory action.HupA has been found to improve cognitivedeficits in a broad range of animal models.HupA possesses the ability to protectcells against hydrogen peroxide,β-amyloid protein (or peptide),glutamate,ischemia and staurosporine-induced cytotoxicity and apoptosis.These protec-tive effects are related to its ability to attenuate oxidative stress,regulate theexpression of apoptotic proteins Bcl-2.Bax,P53,and caspase-3,protectmitochondria,upregulate nerve growth factor and its receptors,and interfere withamyloid precursor protein metabolism.Antagonizing effects of HupA on N-me-thyl-D-aspartate receptors and potassium currents may also contribute to itsneuroprotection as well.Pharmacokinetic studies in rodents,canines,and healthyhuman volunteers indicated that HupA was absorbed rapidly,distributed widelyin the body,and eliminated at a moderate rate with the property of slow andprolonged release after oral administration.Animal and clinical safety tests showedthat HupA had no unexpected toxicity,particularly the dose-limiting hepalotoxic-ity induced by tacrine.The phase Ⅳ clinical trials in China have demonstratedthat HupA significantly improved memory deficits in elderly people with benignsenescent forgetfulness,and patients with Alzheimer disease and vasculardementia,with minimal peripheral cholinergic side effects and no unexpectedtoxicity.HupA can also be used as a protective agent against organophosphateintoxication. Huperzine A (HupA),a novel alkaloid isolated flom the Chinese herb Huperziaserrata,is a potent,highly specific and reversible inhibitor of acetylcholinesterase(ACHE).Compared with tacrine,donepezil,and rivastigmine,HupA has betterpenetration through the blood-brain barrier, H1A possesses the ability to protect cells against hydrogen peroxide, β-amyloid protein (or peptide), -induced cytotoxicity and apoptosis.These protec-tive effects are related to its ability to attenuate oxidative stress,regulate the expression of apoptotic proteins Bcl-2.Bax,P53,and caspase-3,protectmitochondria,upregulate nerve growth factor and its receptors,and Interfere withamyloid precursor protein metabolism.Antagonizing effects of HupA on N-me-thyl-D-aspartate receptors and potassium currents may also contributed to itsneurose Oprotection as well.Pharmacokinetic studies in rodents,canines,and healthyhuman volunteers indicated that HupA was administered rapidly, distributed widelyin the body,and eliminated at a moderate rate with the property of slow and prolonged release after oral administration.Animal and clinical safety tests showedthat HupA单词haty no toxicity, specifically the dose-limiting hepalotoxic-ity induced by tacrine.The phase IV clinical trials in China have revealedthat HupA significantly improved memory deficits in elderly people with benignsenescent forgetfulness, and patients with Alzheimer disease and vasculardementia,with minimal peripheral cholinergic Side effects and no toxic toxicity. HupA can also be used as an protective agent against organophosphateintoxication.