基于网络药理学的蒲黄对血瘀证的作用靶点与代谢通路研究

Study on Targets and Metabolic Pathways of Pollen typhae on Blood Stasis Syndrome Based on Network Pharmacology

关键词:  蒲黄  网络药理学  血瘀证  靶点  分子对接

Key words:  Pollen typhae  network pharmacology  blood stasis syndrome  target  molecular docking

摘要:

本研究利用网络药理学探讨蒲黄（Pollen typhae）治疗血瘀证的作用靶点与代谢通路。研究首先通过PharmGKB、TTD和CTD数据库筛选出与血瘀证相关的靶点；接着利用String平台构建蛋白质相互作用（PPI）网络，并挖掘PPI网络中潜在的蛋白质功能模块，通过Metascape平台分析蒲黄活性成分作用靶点所参与的生物过程及通路；然后采用Cytoscape3.7.2软件构建成分-靶点网络、疾病-靶点网络、成分-靶点-通路网络；最后通过AutoDock Vina软件将蒲黄活性成分、阳性药阿司匹林（Aspirin）与核心靶点进行分子对接验证，并比较各自之间的对接强度。结果表明，槲皮素、山奈酚、异鼠李素、异鼠李素-3-O-新橙皮苷等在参与的成分-靶点网络、疾病-靶点网络、成分-靶点-通路网络中联系密切，其与人体相互作用强，可能是治疗血瘀证的活性成分；核心作用靶点有血管内皮生长因子（VEGFA）、蛋白激酶（AKT1）、雌激素受体（ESR1）、肿瘤坏死因子（TNF）、转录因子（JUN）、有丝分裂原激活蛋白激酶14（MAPK14）等。蒲黄治疗血瘀证的生物学通路主要涉及VEGF信号通路（VEGF signaling pathway），IL-17信号通路（IL-17 signaling pathway），NF-κB信号通路（NF-kappa B signaling pathway）等，其治疗方面主要涉及血管内皮生长因子、血管功能和血液循环等。分子对接验证显示，活性成分和作用靶点的结合能小于-5的占85.88％，即大部分靶点与槲皮素、山奈酚、异鼠李素、异鼠李素-3-O-新橙皮苷的结合活性较好；而Aspirin与靶点的结合强度较蒲黄活性成分异鼠李素-3-O-新橙皮苷、（2R）-5，7-二羟基-2-（4-羟基苯基）苯并吡喃-4-酮、儿茶素和表儿茶素的差。通过网络药理学初步揭示蒲黄多成分、多靶点、多通路的作用特点，预测了蒲黄治疗血瘀证的可能作用靶点和代谢通路；且从分子对接结果来看，蒲黄活性成分异鼠李素-3-O-新橙皮苷、（2R）-5，7-二羟基-2-（4-羟基苯基）苯并吡喃-4-酮、儿茶素和表儿茶素等与核心靶点的对接效果均优于阳性药Aspirin。

Abstract:

The targets and metabolic pathways of Pollen typhae were explored to treat blood stasis syndrome by network pharmacology in this study.Firstly,the targets related to blood stasis syndrome were screened out though PharmGKB,TTD and CTD databases.Then,the protein-protein interaction (PPI) network was constructed by String platform,and the potential protein function modules in PPI network were mined.The biological processes and pathways involved in the targets of active components of Pollen typhae were analyzed by Metascape platform.And Cytoscape3.7.2 software was used to construct the network of ingredient-target,disease-target and ingredient-target-pathway.Finality,AutoDock Vina software was used to verify the molecular docking of active ingredients,Aspirin and core targets,and the docking strength between them was compared.The results showed that quercetin,kaempferol,isorhamnetin and isorhamnetin 3-O-neohesperidin were closely related in the participating ingredient-target network,disease-target network and ingredient-target-pathway network.And they had strong interaction with the human body,which might be active ingredients in the treatment of blood stasis syndrome.The core targets included vascular endothelial growth factor (VEGFA),protein kinase (AKT1),estrogen receptor (ESR1),tumor necrosis factor (TNF),transcription factor (JUN) and mitogen-activated protein kinase 14 (MAPK14),etc.The biological pathways of Pollen typhae in the treatment of blood stasis syndrome mainly involved VEGF signaling pathway,IL-17 signaling pathway and NF-kappa B signaling pathway,and its treatment mainly involved vascular endothelial growth factor,vascular function and blood circulation.Molecular docking verification showed that the binding energy of active ingredients and targets less than-5 accounted for 85.88%,that is,most of the targets had good binding activity with quercetin,kaempferol,isorhamnetin and isorhamnetin-3-O-neohesperidin.While the binding strength of aspirin to the target was lower than that of the active ingredients of Pollen typhae:isorhamnetin-3-O-neohesperidin,(2R)-5,7-dihydroxy-2-(4-hydroxyphenyl) benzopyran-4-one,catechin and epicatechin.The characteristics of multi-ingredient,multi-target and multi-pathway of Pollen typhae were preliminarily revealed by network pharmacology,and the main possible targets and metabolic pathways of Pollen typhae in the treatment of blood stasis syndrome were predicted.Moreover,according to the molecular docking results,isorhamnetin-3-O-neohesperidin,(2R)-5,7-dihydroxy-2-(4-hydroxyphenyl) benzopyran-4-one,catechin and epicatechin were the active components of Pollen typhae, and their docking effect with the core target was better than that of aspirin.