Progress in studies of huperzine A,a natural cholinesterase inhibitor from Chinese herbal medicine
Progress in studies of huperzine A,a natural cholinesterase inhibitor from Chinese herbal medicine作者机构:State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China
出 版 物:《Acta Pharmacologica Sinica》 (中国药理学报(英文版))
年 卷 期:2006年第27卷第1期
页 面:1-26页
核心收录:
学科分类:1008[医学-中药学(可授医学、理学学位)] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学]
基 金:Project supported in part by the grants from Ministry of Science and Technology of China(G1998051110,G1998051115.2004CB518907) the National Natural Science Foundation of China(№ 39170860,39770846,3001161954.30123005.30271496.and 30572169)
主 题:huperzine A Alzheimer disease acetylcholinesterase cholinesterase inhibitors cognitive enhancer neuroprotect agents oxidative stress apoptosis
摘 要: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 *** has been found to improve cognitivedeficits in a broad range of animal *** possesses the ability to protectcells against hydrogen peroxide,β-amyloid protein (or peptide),glutamate,ischemia and staurosporine-induced cytotoxicity and *** protec-tive effects are related to its ability to attenuate oxidative stress,regulate theexpression of apoptotic proteins ***,P53,and caspase-3,protectmitochondria,upregulate nerve growth factor and its receptors,and interfere withamyloid precursor protein *** effects of HupA on N-me-thyl-D-aspartate receptors and potassium currents may also contribute to itsneuroprotection as *** 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 *** and clinical safety tests showedthat HupA had no unexpected toxicity,particularly the dose-limiting hepalotoxic-ity induced by *** 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 *** can also be used as a protective agent against organophosphateintoxication.