摘要
目的:基于网络药理学技术研究西红花抗抑郁的药效物质基础及作用机制。方法:应用中药系统药理学(TCMSP)数据库和分析平台结合文献获取西红花主要活性成分,应用中药分子机制生物信息学分析工具(BATMAN-TCM)获取活性成分的作用靶点,从DrugBank数据库和TTD数据库搜索抑郁症相关靶点,取交集后即得预测靶点。利用String数据库和Cytoscape软件构建"化学成分-关键靶点"网络和蛋白相互作用(PPI)网络,筛选出关键成分和关键靶点,并进行GO生物功能注释和KEGG通路分析。应用SwissDock进行分子对接验证。结果:筛选出西红花抗抑郁作用的5个关键活性成分(槲皮素、西红花酸、山柰酚、藏红花醛、异鼠李素)和21个关键靶点,涉及与突触传递相关的多巴胺摄取、单胺转运等生物过程,作用机制与尼古丁成瘾、多巴胺能神经突触、Ca2+信号通路、5-羟色胺能突触、神经活性配体-受体相互作用、cAMP信号通路等有关。西红花酸和藏红花醛与关键靶点5-羟色胺受体1A(HTR1A)的分子对接效果最好。结论:西红花抗抑郁的主要成分是西红花酸和藏红花醛,HTR1A是其主要作用靶点。
Objective: To study the pharmacodynamic material basis and mechanisms of Croci Stigma on anti-depression based on network pharmacology. Methods: The main active components of Croci Stigma were obtained by TCM System Pharmacology(TCMSP) database and analysis platform combined with literatures, the action targets of active components were obtained by Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM). The depression-related targets were searched from DrugBank database and TTD database, and the predicted targets were obtained after the intersection. The "chemical components-key targets" network and the protein-protein interaction(PPI) network were constructed by String database and Cytoscape software, the key components and targets were screened out, and GO biological function annotation and KEGG pathway analysis were carried out. The molecular docking based on SwissDock was used for verification. Results: Five key active components(quercetin, crocetin, kaempferol, safranal and isorhamnetin) and twenty-one key targets in antidepressant effects of Croci Stigma were screened out, which involved biological processes related to synaptic transmission, such as dopamine uptake and monoamine transport. The mechanisms were related to nicotine addiction, dopaminergic synapse, Ca2+ signaling pathway, serotonergic synapse, neuroactive ligand-receptor interaction, cAMP signaling pathway and so on. The docking effects of crocetin and safranal with 5-hydroxytryptamine receptor 1 A(HTR1 A) were the best. Conclusion: The main antidepressant components of Croci Stigma are crocetin and safranal, and HTR1 A is the main target.
作者
俞婷
邢越阳
朱国琴
YU Ting;XING Yueyang;ZHU Guoqin(Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;SPH Xing Ling Sci.&Tech.Pharmaceutical Co.,Ltd.,Shanghai 201703,China)
出处
《上海中医药大学学报》
CAS
2020年第3期70-75,共6页
Academic Journal of Shanghai University of Traditional Chinese Medicine
基金
上海市国资委企业技术创新和能级提升项目(2018010)。
