酸枣仁中Coclaurine的分离及运用网络药理学探讨其抗抑郁的作用机制

Separation of Coclaurine from Ziziphi Spinosae Semen and Discussion on Its Antidepressant Mechanism by Network Pharmacology

目的:分离并探讨酸枣仁中生物碱成分Coclaurine的抗抑郁作用机制。方法:采用制备型高效液相色谱法(P-HPLC)分离得酸枣仁生物碱成分Coclaurine,并对其进行类药性预测。利用PharmMapper和DrugBank数据库筛选Coclaurine抗抑郁的潜在靶点;采用MAS 3.0生物分子功能软件获取潜在靶点和通路的相关信息;采用Cytoscape软件构建治疗抑郁症的"Coclaurine-靶点-通路"网络模型;采用分子对接软件Autodock Tools 1.5.6将预测得到的蛋白靶点与Coclaurine进行分子对接分析,研究Coclaurine分子与靶蛋白的相互作用。结果:采用质谱(MS)、核磁共振波谱(NMR)鉴定为酸枣仁生物碱单体Coclaurine,且其有较好的类药性。Coclaurine可能通过Glycogen synthase kinase-3 beta、Cystathionine beta-synthase等6个抑郁症相关靶点调控MAPK signaling pathway、VEGF signaling pathway、Insulin signaling pathway等39条信号通路从而参与调节免疫、炎症反应、脂质代谢、细胞凋亡等过程来发挥治疗抑郁症及其并发症的作用。结论:研究结果为为Coclaurine治疗抑郁症提供了理论依据。

Objective:To isolate and discuss the antidepressant mechanism of Coclaurine from Ziziphi Spinosae Semen.Methods:Coclaurine in Ziziphi Spinosae Semen was isolated by preparative high performance liquid chromatography(P-HPLC)and its drug-like properties were predicted.The PharmMapper and DrugBank databases were used to screen the potential targets of Coclaurine anti-depression.MAS 3.0 biomolecule function software was used to obtain information on potential targets and pathways.Cytoscape software was used to construct a"Coclaurine-target-path"network model for treating depression.Molecular docking software Autodock Tools 1.5.6 was used to perform molecular docking analysis of the predicted protein target and Coclaurine.The interaction between Coclaurine molecules and target proteins was studied.Results:Mass spectrometry(MS)and nuclear magnetic resonance spectroscopy(NMR)were used to identify Coclaurine,an alkaloid component from Ziziphi Spinosae Semen,which had good drug-like properties.Coclaurine may regulate thirty-nine signaling pathways including MAPK signaling pathway,VEGF signaling pathway and Insulin signaling pathway through six depression-related targets including Glycogen synthase kinase-3 beta and Cystathionine beta-synthase to participate in the process of immune,inflammatory,lipid metabolism,cell apoptosis and other processes to play a role in the treatment of depression and its complications.Conclusion:The study provides theoretical basis for Coclaurine to treat depression.