摘要
通过网络药理学结合分子对接技术研究地黄抗抑郁的有效成分及作用机制。利用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱(UPLC-Q-Orbitrap HRMS)技术鉴定地黄主要成分,利用SwissTargetPrediction平台预测药物成分相关靶点,利用GeneCards、OMIM、TTD数据库搜集与抑郁症相关联的靶点,利用STRING数据库构建靶点蛋白相互作用网络;通过Metascape数据库进行GO功能分析及KEGG通路富集分析。借助Cytoscape 3.7.2软件构建"成分-靶点-疾病"以及"成分-靶点-通路"网络,分析获取网络中的关键靶点与其对应成分,并利用分子对接进行初步验证。地黄包括环烯醚萜类、紫罗兰酮类、苯乙醇苷类三大类85个化学成分。网络分析结果显示,地黄抗抑郁的主要成分为梓醇、密力特苷、genameside C、栀子新苷、6-O-对香酰基筋骨草醇、京尼平龙胆双糖苷、jiocarotenoside A1、neo-rehmannioside、地黄苷C、吉奥诺苷C、吉奥诺苷D、毛蕊花糖苷、地黄苷、肉苁蓉苷F、leucosceptoside A 15个化合物,对应AKT1、ALB、IL6、APP、MAPK1、CXCL8、VEGFA、TNF、HSP90AA1、SIRT1、CNR1、CTNNB1、OPRM1、DRD2、ESR1、SLC6A4这16个抗抑郁核心靶点。分子对接发现,氢键和疏水作用可能是其主要作用的形式。地黄抗抑郁症的重要靶点显著富集于神经活性配体-受体相互作用、神经退行性病变-多种疾病通路、磷脂酰肌醇3-激酶/蛋白激酶B通路、5-羟色胺能突触、阿尔茨海默病等24个信号通路中。
This study aimed to explore the anti-depressant components of Rehmanniae Radix and its action mechanism based on network pharmacology combined with molecular docking.The main components of Rehmanniae Radix were identified by ultra-high performance liquid chromatography-quadrupole/Orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap HRMS),and the related targets were predicted using SwissTargetPrediction.Following the collection of depression-related targets from GeneCards,OMIM and TTD,a protein-protein interaction(PPI)network was constructed using STRING.GO and KEGG pathway enrichment analysis was performed by Metascape.Cytoscape 3.7.2 was used to construct the networks of"components-targets-disease"and"components-targets-pathways",based on which the key targets and their corresponding components were obtained and then preliminarily verified by molecular docking.Rehmanniae Radix contained 85 components including iridoids,ionones,and phenylethanoid glycosides.The results of network analysis showed that the main anti-depressant components of Rehmanniae Radix were catalpol,melittoside,genameside C,gardoside,6-O-p-coumaroyl ajugol,genipin-1-gentiobioside,jiocarotenoside A1,neo-rehmannioside,rehmannioside C,jionoside C,jionoside D,verbascoside,rehmannioside,cistanoside F,and leucosceptoside A,corresponding to the following 16 core anti-depression targets:AKT1,ALB,IL6,APP,MAPK1,CXCL8,VEGFA,TNF,HSP90 AA1,SIRT1,CNR1,CTNNB1,OPRM1,DRD2,ESR1,and SLC6 A4.As revealed by molecular docking,hydrogen bonding and hydrophobicity might be the main action forms.The key anti-depression targets of Rehmanniae Radix were concentrated in 24 signaling pathways,including neuroactive ligand-receptor interaction,neurodegenerative disease-multiple diseases pathway,phosphatidylinositol 3-kinase/protein kinase B pathway,serotonergic synapse,and Alzheimer′s disease.
作者
韩德恩
岳中胜
李红伟
刘改枝
蔡邦荣
田萍
HAN De-en;YUE Zhong-sheng;LI Hong-wei;LIU Gai-zhi;CAI Bang-rong;TIAN Ping(School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,China;Henan Academy of Chinese Medicine,Zhengzhou 450004,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2022年第4期1051-1063,共13页
China Journal of Chinese Materia Medica
基金
河南省中医药研究院基本业务费课题(2004823)。
