Gu Jia-Ming, Xue Hui, Xue Ao, Jiang Jing, Geng Fang, Zhao Ji-Hui, Yang Bo, Zhang Ning
School of Pharmacy, Heilongjiang University of Chinese Medicine Harbin 150040, China.
School of Pharmacy, Heilongjiang University of Chinese Medicine Harbin 150040, China Jiamusi College, Heilongjiang University of Chinese Medicine Jiamusi 154007, China.
Zhongguo Zhong Yao Za Zhi. 2023 Aug;48(15):4039-4045. doi: 10.19540/j.cnki.cjcmm.20230303.401.
This study aimed to investigate the mechanism of Psoraleae Fructus in improving the learning and memory ability of APP/PS1 mice by serum metabolomics, screen the differential metabolites of Psoraleae Fructus on APP/PS1 mice, and reveal its influence on the metabolic pathway of APP/PS1 mice. Thirty 3-month-old APP/PS1 mice were randomly divided into a model group and a Psoraleae Fructus extract group, and another 15 C57BL/6 mice of the same age were assigned to the blank group. The learning and memory ability of mice was evaluated by the Morris water maze and novel object recognition tests, and metabolomics was used to analyze the metabolites in mouse serum. The results of the Morris water maze test showed that Psoraleae Fructus shortened the escape latency of APP/PS1 mice(P<0.01), and increased the number of platform crossing and residence time in the target quadrant(P<0.01). The results of the novel object recognition test showed that Psoraleae Fructus could improve the novel object recognition index of APP/PS1 mice(P<0.01). Eighteen differential metabolites in serum were screened out by metabolomics, among which the levels of arachidonic acid, tryptophan, and glycerophospholipid decreased after drug administration, while the levels of glutamyltyrosine increased after drug administration. The metabolic pathways involved included arachidonic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, linoleic acid metabolism, α-linolenic acid metabolism, and glycerolipid metabolism. Therefore, Psoraleae Fructus can improve the learning and memory ability of APP/PS1 mice, and its mechanism may be related to the effects in promoting energy metabolism, reducing oxidative damage, protecting central nervous system, reducing neuroinflammation, and reducing Aβ deposition. This study is expected to provide references for Psoraleae Fructus in the treatment of Alzheimer's disease(AD) and further explain the mechanism of Psoraleae Fructus in the treatment of AD.
本研究旨在通过血清代谢组学探讨补骨脂改善APP/PS1小鼠学习记忆能力的机制，筛选补骨脂对APP/PS1小鼠的差异代谢物，并揭示其对APP/PS1小鼠代谢途径的影响。将30只3月龄的APP/PS1小鼠随机分为模型组和补骨脂提取物组，另将15只同年龄的C57BL/6小鼠作为空白组。采用Morris水迷宫和新物体识别试验评估小鼠的学习记忆能力，运用代谢组学分析小鼠血清中的代谢物。Morris水迷宫试验结果显示，补骨脂缩短了APP/PS1小鼠的逃避潜伏期（P<0.01），并增加了穿越平台次数和在目标象限的停留时间（P<0.01）。新物体识别试验结果表明，补骨脂可提高APP/PS1小鼠的新物体识别指数（P<0.01）。代谢组学筛选出18种血清差异代谢物，给药后花生四烯酸、色氨酸和甘油磷脂水平降低，而谷氨酰酪氨酸水平升高。涉及的代谢途径包括花生四烯酸代谢、甘油磷脂代谢、色氨酸代谢、亚油酸代谢、α-亚麻酸代谢和甘油脂代谢。因此，补骨脂可改善APP/PS1小鼠的学习记忆能力，其机制可能与促进能量代谢、减少氧化损伤、保护中枢神经系统、减轻神经炎症及减少Aβ沉积有关。本研究有望为补骨脂治疗阿尔茨海默病（AD）提供参考，并进一步阐释补骨脂治疗AD的机制。
