Park C H, Kim S H, Choi W, Lee Y J, Kim J S, Kang S S, Suh Y H
Department of Pharmacology, College of Medicine, Seoul, South Korea.
Planta Med. 1996 Oct;62(5):405-9. doi: 10.1055/s-2006-957926.
To find a new compound with antiamnesic activity, we screened 29 natural products for their abilities to inhibit acetylcholinesterase and reverse scopolamine-induced amnesia. Among the plants tested Evodia rutaecarpa Bentham showed a strong inhibitory effect on acetylcholinesterase in vitro and an anti-amnesic effect in vivo. By sequential fractionation of E. rutaecarpa, the active component was finally identified as dehydroevodiamine hydrochloride (DHED). DHED inhibited acetylcholinesterase activity in a dose-dependent and non-competitive manner. The IC50 value of DHED is 37.8 microM. A single administration of DHED to rats (6.25 mg/kg) significantly reversed the scopolamine-induced memory impairment in a passive avoidance test. The antiamnesic effect of DHED was more potent than that of tacrine which is the only drug for Alzheimer's disease approved by FDA. This potent antiamnesic effect of DHED was thought to be due to the combined effects of acetylcholinesterase inhibition and the known cerebral blood flow enhancement. These results indicate that DHED has novel anti-cholinesterase and antiamnesic activities and might have therapeutic potential in various disorders including Alzheimer's disease.
为了找到一种具有抗遗忘活性的新化合物，我们筛选了29种天然产物，检测它们抑制乙酰胆碱酯酶和逆转东莨菪碱诱导的遗忘的能力。在所测试的植物中，吴茱萸在体外对乙酰胆碱酯酶表现出强烈的抑制作用，在体内具有抗遗忘作用。通过对吴茱萸进行逐步分离，最终确定活性成分是盐酸去氢吴茱萸碱（DHED）。DHED以剂量依赖性和非竞争性方式抑制乙酰胆碱酯酶活性。DHED的IC50值为37.8微摩尔。在被动回避试验中，给大鼠单次注射DHED（6.25毫克/千克）可显著逆转东莨菪碱诱导的记忆损伤。DHED的抗遗忘作用比他克林更强，他克林是美国食品药品监督管理局批准的唯一用于治疗阿尔茨海默病的药物。DHED这种强大的抗遗忘作用被认为是由于其抑制乙酰胆碱酯酶和已知的增加脑血流量的联合作用。这些结果表明，DHED具有新型抗胆碱酯酶和抗遗忘活性，在包括阿尔茨海默病在内的各种疾病中可能具有治疗潜力。
