Japanese Huperzia serrata extract and the constituent, huperzine A, ameliorate the scopolamine-induced cognitive impairment in mice

Huperzia serrata has been used as a Chinese folk medicine for many years. It contains huperzine A, which has a protective effect against memory deficits in animal models; however, it is unclear if H. serrata extract exerts any effects in Alzheimer’s disease (AD) models. We used H. serrata collected in Japan and determined its huperzine A content using HPLC. We determined its inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity. H. serrata extract (30 mg/kg/day) and donepezil (10 mg/kg/day) were orally administrated for 7 days. After repeated administration, we performed the Y-maze and passive avoidance tests. H. serrata extract contained 0.5% huperzine A; H. serrata extract inhibited AChE, but not BuChE. H. serrata extract ameliorated cognitive function in mice. These results indicate that Japanese H. serrata extract ameliorates cognitive function deficits by inhibiting AChE. Therefore, H. serrata extract may be valuable for the prevention or treatment of dementia in AD.蛇足石杉（Huperzia serrata）作为中国民间药物已有多年应用历史。其所含的石杉碱甲（huperzine A）对动物模型的记忆缺损具有保护作用，但目前尚不清楚蛇足石杉提取物是否对阿尔茨海默病（Alzheimer’s disease, AD）模型具有相关作用。本研究使用采集自日本的蛇足石杉，采用高效液相色谱（HPLC）法测定其石杉碱甲含量，并检测其对乙酰胆碱酯酶（acetylcholinesterase, AChE）与丁酰胆碱酯酶（butyrylcholinesterase, BuChE）活性的抑制作用。以30 mg/kg/天的蛇足石杉提取物与10 mg/kg/天的多奈哌齐（donepezil）连续灌胃给药7天。反复给药后，开展Y迷宫（Y-maze）与被动回避试验。结果显示，蛇足石杉提取物中石杉碱甲含量为0.5%；该提取物可抑制乙酰胆碱酯酶活性，但对丁酰胆碱酯酶活性无影响。蛇足石杉提取物可改善小鼠的认知功能。上述结果表明，日本产蛇足石杉提取物通过抑制乙酰胆碱酯酶活性改善认知功能缺损。因此，蛇足石杉提取物或可用于阿尔茨海默病相关痴呆的预防或治疗。