Abstract Context The methanol extracts from Hippeastrum reticulatum (L'Hér.) Herb. (Amaryllidaceae) (HR) display acetylcholinesterase inhibitory (AChEI) activity. Objective AChEI of alkaloids isolated from HR bulbs and the ameliorating effects of the alkaloid fraction (AHR) on memory and cognitive dysfunction in scopolamine-treated mice were investigated. Materials and methods Alkaloids were isolated by column chromatography and identified by spectroscopy. AChEI was evaluated using the modified Ellman’s method. Sixty Swiss male mice were randomly divided into six groups, received samples for 15 days. Normal group received saline, scopolamine-treated group scopolamine (1.5 mg/kg, intraperitoneal injection). Test groups received AHR (5, 10 and 15 mg/kg, per os) and positive control group donepezil (5 mg/kg, per os), administered 1 h before the test, scopolamine was injected 30 min prior to testing. The cognitive-enhancing activity of AHR against scopolamine-induced memory impairments was investigated using Y-maze, the novel object recognition test (NORT) and the Morris water maze (MWM) test. Results Seven alkaloids were isolated for the first time from the genus Hippeastrum: trans-dihydronarciclasine (1), N-chloromethylnarcissidinium (2), narciprimin (3), narciclasine-4-O-β-d-xylopyranoside (4), N-methyltyramine (5), 3β,11α-dihydroxy-1,2-dehydrocrinane (6) and brunsvigine (7); three are new compounds (2, 5, 6). Among them, 2–3 and 5–6 showed AChEI in vitro with IC50 values of 29.1, 46.4, 70.1 and 104.5 µg/mL, respectively. The anti-AChEI of 2, 5 and 6 are reported for the first time. In in vivo test, AHR (15 mg/kg) significantly increased in spontaneous alternation performance in the Y-maze test (p < 0.01), it significantly increased the time spent exploring the novel object (p < 0.05) comparison with scopolamine-treated group. The administration of AHR at doses 10 and 15 mg/kg significantly decreased escapes latency and swimming distance to the platform on day 6 compared to these in day 1 (p < 0.01 and p < 0.05, respectively). Conclusions AHR could be a potential candidate of future trials for treatment of memory and cognitive dysfunction in Alzheimer’s disease.

中文翻译：

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朱顶红对东莨菪碱诱导的阿尔茨海默病动物模型记忆、空间学习和物体识别的影响

摘要 上下文 Hippeastrum reticulatum (L'Hér.) Herb 的甲醇提取物。(石蒜科) (HR) 显示乙酰胆碱酯酶抑制 (AChEI) 活性。目的 研究从 HR 球茎中分离的生物碱的 AChEI 以及生物碱组分 (AHR) 对东莨菪碱治疗小鼠记忆和认知功能障碍的改善作用。材料与方法 生物碱通过柱层析分离和光谱鉴定。使用改良的 Ellman 方法评估 AChEI。60 只瑞士雄性小鼠被随机分成六组，接受样品 15 天。正常组给予生理盐水，东莨菪碱治疗组给予东莨菪碱（1.5 mg/kg，腹腔注射）。测试组接受 AHR（5、10 和 15 毫克/公斤，口服）和阳性对照组多奈哌齐（5 毫克/公斤，口服），试验前 1 小时给药，试验前 30 分钟注射东莨菪碱。使用 Y 迷宫、新物体识别测试 (NORT) 和莫里斯水迷宫 (MWM) 测试研究了 AHR 对东莨菪碱诱导的记忆障碍的认知增强活性。结果首次从朱顶红属中分离得到7种生物碱：反式二氢水仙花苷(1)、N-氯甲基水仙花素(2)、水仙花素(3)、水仙花素-4-O-β-d-吡喃木糖苷(4)、N-甲基酪胺 (5)、3β,11α-二羟基-1,2-脱氢克林烷 (6) 和 brunsvigine (7)；三是新化合物（2、5、6）。其中，2-3 和 5-6 在体外表现出 AChEI，IC50 值分别为 29.1、46.4、70.1 和 104.5 µg/mL。2、5和6的抗AChEI是首次报道。在体内试验中，AHR (15 mg/kg) 在 Y 迷宫测试中的自发交替性能显着增加 (p < 0.01)，与东莨菪碱治疗组相比，它显着增加了探索新物体的时间 (p < 0.05)。与第 1 天相比，在第 6 天以 10 和 15 mg/kg 的剂量施用 AHR 显着降低了逃逸潜伏期和到平台的游泳距离（分别为 p < 0.01 和 p < 0.05）。结论 AHR 可能是未来治疗阿尔茨海默病记忆和认知功能障碍试验的潜在候选者。与第 1 天相比，在第 6 天以 10 和 15 mg/kg 的剂量施用 AHR 显着降低了逃逸潜伏期和到平台的游泳距离（分别为 p < 0.01 和 p < 0.05）。结论 AHR 可能是未来治疗阿尔茨海默病记忆和认知功能障碍试验的潜在候选者。与第 1 天相比，在第 6 天以 10 和 15 mg/kg 的剂量施用 AHR 显着降低了逃逸潜伏期和到平台的游泳距离（分别为 p < 0.01 和 p < 0.05）。结论 AHR 可能是未来治疗阿尔茨海默病记忆和认知功能障碍试验的潜在候选者。