基于网络药理学及分子对接验证探讨退热解毒灵清热抗炎机制

目的：运用网络药理学的方法来筛选退热解毒灵清热抗炎的作用靶点，并且探讨其作用机制。方法：使用TCMSP数据库查询到板蓝根、柴胡、连翘、甘草的主要化学成分以及作用靶点，根据ADME筛选出祛白颗粒的活性成分并且搜集其靶点，通过Genecards、OMIM、TTD、DRUGBANK、DisGeNET数据库搜集相关疾病靶点，使用STRING构建蛋白质间的相互作用网络，接着利用Metascape进行GO功能富集分析和KEGG通路分析，最后利用Cytoscape构建成分-靶点-通路网络。最后进行分子对接验证。结果：退热解毒灵清热抗炎的主要成分有67种，核心靶点有65种，包括PTGS2，HSP90AA1，NOS2，CAMKK2，PTGS1等。GO和KEGG富集结果显示，退热解毒灵清热抗炎的生物学通路主要有神经活性配体—受体相互作用、胆碱能突触、人类巨细胞病毒感染、IL-17信号通路等等。结论：本研究初步揭示了退热解毒灵清热抗炎的多成分、多靶点、多通路的作用机制，为退热解毒灵在临床上的进一步应用提供理论基础。

Mechanism of antipyretic and anti-inflammation actions of Tuire Jieduling based upon network pharmacology and molecular docking methods

OBJECTIVE To employ the method of network pharmacology for screening the targets of antipyretic and anti-inflammatory effects of Tuire Jieduling and elucidate its mechanism of action. METHODS The database of TCMSP was accessed for searching for major chemical components and targets of Isatidis Radix, Bupleuri Radix and Forsythiae Fructus Glycyrrhizae Radix et Rhizoma. According to the ADME value, the active components of Tuire Jieduling were screened and their targets identified. Through the databases of Genecards, OMIM, TTD, DRUGBANK and DisGeNET, the relevant disease targets were collected. The database of STRING was utilized for constructing a protein-protein interaction network, Metascape database for GO function enrichment and KEGG pathway analyses and then Cytoscape software for constructing a component-target-pathway network. Finally molecular docking verification was performed. RESULTS The major components of Tuire Jieduling for antipyretic and anti-inflammatory included 67 kinds of medicarpin, 7-methoxy-2-methyl isoflavone, octalupine, wogonin and formononetin, etc. and 65 core targets, including PTGS2, HSP90AA1, NOS2, CAMKK2 and PTGS1, etc. The enrichment results of GO/KEGG indicated that the biological pathways of antipyretic and anti-inflammation encompassed mainly neuroactive ligand-receptor interaction, cholinergic synapse, human cytomegalovirus infection and IL-17 signaling pathway, etc. CONCLUSION This preliminary study reveals the multi-component, multi-target and multi-pathway mechanism of anti-inflammatory and anti-inflammatory effects of Tuire Jieduling. Thus it provides theoretical rationales for further clinical application of Tuire Jieduling.