基于网络药理学的香附抗抑郁作用机制研究
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摘要
目的基于网络药理学方法研究香附多成分-多靶点-多途径的抗抑郁潜在作用机制。方法通过中药系统药理学分析平台(TCMSP)数据库、文献挖掘和本实验室已有研究收集香附化学成分,并依据类药原则进行筛选。使用PhamMapper和DrugBank数据库进行靶点预测和筛选,通过MAS 3.0及KEGG通路注释分析香附抗抑郁效应化学成分的作用通路,采用Cytoscape 3.6.1软件构建"化合物-核心靶点-通路"网络,预测其抗抑郁药效成分及相关作用靶点。结果香附中的69个化合物作用于103个靶点,29个核心靶点。构建的"化合物-核心靶点-代谢通路"网络预测发现,香附中48个化学成分直接或间接作用于15个核心靶点,8条抑郁相关代谢通路,主要涉及细胞过程、对应激的应答等生物过程,通过调节黏附斑、神经营养因子、血管内皮生长因子(VEGF)、促性腺激素释放激素(GnRH)、NOD样受体、胰岛素、趋化因子、ErbB信号通路发挥抗抑郁作用。结论网络药理学分析结果初步揭示了香附以多成分、多靶点、多通路的协同作用方式发挥抗抑郁效应机制。
Objective To explore the antidepressant mechanism of Cyperus rotundus L.based on network pharmacology.Methods Compounds of C.rotundus was collected by retrieving throuh TCMSP database,the literatures mining,and existing research of laboratory.The ingredients selected as the research objects were screened according to the generic drug principle.PhamMapper and DrugBank database were then applied to predict the targets.MAS 3.0 software and KEGG pathways were used to annotate the information of targets.Cytoscape 3.6.1 track software was used to construct "ingredients-targets-pathways" network to predict the components and related targets related to antidepressant efficacy.Results Targets predicting analysis showed that 103 targets and 29 core targets were interacted with 69 compounds of C.rotundus.The network analysis indicated that 48 components directly or indirectly interacted with 15 core targets and 8 depression-related metabolic pathways.The above targets were mainly involved in cell processes,responses to stress,and other biological processes,which played an anti-depressive role by regulating the focal adhesion,neurotrophin,VEGF,GnRH,NOD-like receptor,insulin,chemokines,and ErbB signaling pathways.Conclusion The results of network pharmacology analysis preliminarily revealed that the mechanism of anti-depression effect of Cyperus C.rotundus L.through was the synergistic effect of multiple components,multiple targets,and multiple pathways.
Objective To explore the antidepressant mechanism of Cyperus rotundus L.based on network pharmacology.Methods Compounds of C.rotundus was collected by retrieving throuh TCMSP database,the literatures mining,and existing research of laboratory.The ingredients selected as the research objects were screened according to the generic drug principle.PhamMapper and DrugBank database were then applied to predict the targets.MAS 3.0 software and KEGG pathways were used to annotate the information of targets.Cytoscape 3.6.1 track software was used to construct "ingredients-targets-pathways" network to predict the components and related targets related to antidepressant efficacy.Results Targets predicting analysis showed that 103 targets and 29 core targets were interacted with 69 compounds of C.rotundus.The network analysis indicated that 48 components directly or indirectly interacted with 15 core targets and 8 depression-related metabolic pathways.The above targets were mainly involved in cell processes,responses to stress,and other biological processes,which played an anti-depressive role by regulating the focal adhesion,neurotrophin,VEGF,GnRH,NOD-like receptor,insulin,chemokines,and ErbB signaling pathways.Conclusion The results of network pharmacology analysis preliminarily revealed that the mechanism of anti-depression effect of Cyperus C.rotundus L.through was the synergistic effect of multiple components,multiple targets,and multiple pathways.
引文
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[18]Wang Y,Jiang H L,Meng H,et al.Genome-wide transcriptome analysis of hippocampus in rats indicated that TLR/NLR signaling pathway was involved in the pathogenisis of depressive disorder induced by chronic restraint stress[J].Brain Res Bull,2017,134:195-204.
[19]Tervaniemi M H,Katayama S,Skoog T,et al.NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis[J].Sci Rep,2016,6:22745.
[2]段艳霞,李洁,史美育.中药治疗中风后抑郁症用药规律探讨[J].中华中医药学刊,2011,29(6):1419-1421.
[3]王君明,马艳霞,张蓓,等.香附提取物抗抑郁作用研究[J].时珍国医国药,2013,24(4):779-781.
[4]周中流,尹文清,张华林,等.香附化学成分研究[J].中草药,2013,44(10):1226-1230.
[5]季宁平,周莉江,严鑫,等.醋制香附不同提取部位对肝郁血瘀模型大鼠的影响[J].中药与临床,2017,8(2):57-60.
[6]邢心睿,吕狄亚,柴逸峰,等.网络药理学在中药作用机制中的研究进展[J].药学实践杂志,2018,36(2):97-102.
[7]Zhang Y Q,Mao X,Guo Q Y,et al.Network pharmacology-based approaches capture essence of chinese herbal medicines[J].Chin Herb Med,2016,8(2):107-116
[8]贾皓,庞晓丛,赵赢,等.远志治疗阿尔茨海默病的网络药理学作用机制[J].中国新药杂志,2018,27(4):398-404.
[9]李静,高丽,高耀,等.基于网络药理学的款冬花止咳化痰活性成分靶点探究[J].中草药,2018,49(1):179-187.
[10]吴丹,高耀,向欢,等.基于网络药理学的柴胡抗抑郁作用机制研究[J].药学学报,2018,53(2):210-219.
[11]陈志坚,胡璇,刘国道.香附的化学成分及药理作用研究进展[J].安徽农业科学,2017,45(36):113-115.
[12]Ma X H,Lv B,Li P,et al.Identification of"multiple components-multiple targets-multiple pathways"associated with naoxintong capsule in the treatment of heart diseases using UPLC/Q-TOF-MS and network pharmacology[J].Evid Based Complement Alternat Med,2016,2016:9468087.
[13]Hawi Z,Tong J,Dark C,et al.The role of cadherin genes in five major psychiatric disorders:A literature update[J].Am J Med Genet B Neuropsychiatr Genet,2018,177(2):168-180.
[14]Cheng D,Murtaza G,Ma S Y,et al.In silico prediction of the anti-depression mechanism of a herbal formula(tiansi liquid)containing morinda officinalis and cuscuta chinensis[J].Molecules,2017,22(10):1614.
[15]Sasaki K,El Omri A,Kondo S,et al.Rosmarinus officinalis polyphenols produce anti-depressant like effect through monoaminergic and cholinergic functions modulation[J].Behav Brain Res,2013,238(1):86-94.
[16]Gormanns P,Mueller N S,Ditzen C,et al.Phenometranscriptome correlation unravels anxiety and depression related pathways[J].J Psychiatr Res,2011,45(7):973-979.
[17]高耀,高丽,高晓霞,等.基于网络药理学的逍遥散抗抑郁活性成分作用靶点研究[J].药学学报,2015,50(12):1589-1595.
[18]Wang Y,Jiang H L,Meng H,et al.Genome-wide transcriptome analysis of hippocampus in rats indicated that TLR/NLR signaling pathway was involved in the pathogenisis of depressive disorder induced by chronic restraint stress[J].Brain Res Bull,2017,134:195-204.
[19]Tervaniemi M H,Katayama S,Skoog T,et al.NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis[J].Sci Rep,2016,6:22745.
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