【摘要】 目的：采用网络药理学分析结合分子对接、体外细胞实验探讨人参环氧炔醇(PND)治疗阿尔茨海默病的作用机制，并验证其对神经细胞的保护作用。方法：基于PharmMapper、GeneCards、STRING等数据库筛选PND治疗阿尔茨海默病的作用靶点并构建蛋白质相互作用网络，通过GO及KEGG通路富集分析明确特征通路，并利用分子对接技术进行验证。用人神经母细胞瘤SH-SY5Y细胞建立L-谷氨酸诱导的细胞损伤模型，实验组细胞加入不同浓度的PND(10、20、40μmol/L)预处理，采用CCK-8法检测细胞活性，流式细胞术检测细胞凋亡情况。结果：构建PND-核心靶点-特征通路-阿尔茨海默病网络，发现PND调控的重要核心靶点包括ALB、AKT1、EGFR、SRC、CASP3、NFKB1、PTGS2、PPARG等，特征通路涉及EGFR通路、C型凝集素受体信号通路、RAS信号通路、PI3K-Akt信号通路和阿尔茨海默病信号通路；分子对接结果表明PND对CYP3A4、APP、EGFR等靶点具有较好的调控作用。体外细胞实验结果显示，L-谷氨酸诱导的神经损伤模型组SH-SY5Y细胞存活率较对照组降低(P<0.01),20μmol/L PND预处理组细胞存活率高于模型组(P<0.01)；模型组神经细胞总凋亡率为45.23%,10、20、40μmol/L PND预处理组细胞的凋亡率分别为41.34%、36.96%和21.86%，均低于模型组(P<0.05或P<0.01)。结论：PND具有神经保护作用，并可能通过保护神经细胞从而起到治疗阿尔茨海默病的作用。更多还原

【Abstract】 OBJECTIVE: To use network pharmacology analysis together with molecular docking and in vitro cell experiments for evaluating therapeutic potential of ginseng cyclopentadienol(PND) on Alzheimer’s disease,and for understanding its protective effect on neurons. METHODS:Targets of PND in the treatment of Alzheimer ’ s disease were screened based on Pharm Mapper, Gene Cards, STRING and other databases, and a protein interaction network was constructed. Characteristic pathways were identified by GO and KEGG pathway enrichment analysis and then verified by molecular docking technology. An L-glutamate-induced cell injury model was established using human neuroblastoma SH-SY5Y cells. After treatment of these cells with different concentrations of PND(10,20,40 μmol/L), cell activity was detected by CCK-8 method,and apoptosis was detected by flow cytometry. RESULTS: A PND-core target-characteristic pathway-Alzheimer’s disease network was constructed, and the important targets regulated by PND were found to be ALB, AKT1, EGFR, SRC,CASP3, NFKB1, PTGS2, PPARG, etc. Multiple pathways were identified to involve EGFR, C-type lectin receptor signaling,RAS signaling,PI3K-Akt signaling and Alzheimer’s disease signaling. The molecular docking results showed that PND had a good regulatory effect on targets such as CYP3A4,APP,and EGFR. Results from the in vitro cell experiments showed that the survival rate of SH-SY5Y cells in the L-glutamate-induced nerve injury model group was reduced,and the cell survival rate in the 20 μmol/L PND treatment group was higher than that in the model group(P<0.01);the total apoptosis rate of nerve cells in the model group was45.23%,and the apoptosis rates of cells in the 10,20 and 40 μmol/L PND treatment groups were 41.34%,36.96% and 21.86%, respectively, which were lower than those in the model group(P<0.05 or P<0.01).CONCLUSION:PND showed a neuroprotective effect which may be useful for treatment of Alzheimer’s disease.更多还原