苗药重楼解毒方对肛周脓肿术后促愈的网络药理学分子机制研究

Molecular Mechanism of Network Pharmacology of Chonglou Jiedu Formula of Traditional Miao Herbs in Promoting Postoperative Healing of Perianal Abscess

目的:通过网络药理学方法和分子对接技术探讨苗药重楼解毒方熏洗对肛周脓肿术后创面愈合的潜在作用机制。方法:在HERB数据库中搜寻重楼解毒方所用中药分子以及靶点蛋白,在GeneCards和OMIM数据库中检索疾病的靶点,运用Venny 2.1在线获取交集靶点,继而于String数据库中进行PPI分析;在Cytoscape 3.7.1以及Metascape数据库中相继完成可视化网络图与富集分析。根据上述结果完成分子对接。结果:该方共有154个药物活性成分,845个药物作用靶点,1040个疾病作用靶点,药物-疾病交集靶点146个;核心靶点9个,分别为丝氨酸/苏氨酸蛋白激酶(AKT1)、肿瘤坏死因子(TNF)、白介素-6(IL-6)、血管内皮生长因子A(VEGFA)、丝裂原激活蛋白激酶3(MAPK3)、白蛋白(ALB)、转录因子Jun(JUN)、原癌基因酪氨酸蛋白激酶Src(SRC)和表皮生长因子受体(EGFR);富集分析显示,重要信号通路包含PI3K-AKT、AGE-RAGE、MAPK等;分子对接结果显示,核心靶点蛋白与活性小分子的对接值均小于-5.0 kcal/mol,证明结论较为可靠。结论:重楼解毒方熏洗对肛周脓肿术后创面愈合存在多靶点、多成分、多通路的作用机制,其中药物活性成分鱼腥草的槲皮素(Quercetin)、木犀草素(Luteolin)、芹菜素(Apigenin)、三七的吴茱萸次碱(Rutaecarpine)、重楼的重楼皂苷Ⅱ(PolyphyllinⅡ)和靶点AKT1、TNF以及信号通路PI3K-AKT、AGE-RAGE、MAPK等应特别关注,本研究中建立的网络有助于从分子水平到通路水平认知重楼解毒方的作用机制。

Objective To investigate the potential mechanism of Miao herbal fumigation and washing of Chonglou Jiedu Formula on wound healing after perianal abscess operation by means of network pharmacology and molecular docking technology.Methods Herbal molecules and target proteins in Chonglou Jiedu Formula were searched in HERB database,and disease targets were searched in GeneCards and OMIM database.The intersection targets were obtained online by Venny 2.1,and PPI analysis was performed in String database.Visual network diagram and enrichment analysis were performed successively in Cytoscape 3.7.1 and Metascape databases.Molecular docking was completed according to the above results.Results There were 154 active components,845 drug action targets,1040 disease action targets,and 146 drug-disease intersection targets in total.Nine core targets were serine/threonine protein kinase(AKT1),tumor necrosis factor(TNF),interleukin-6(IL-6),vascular endothelial growth factor A(VEGFA),mitogen activated protein kinase 3(MAPK3),albumin(ALB),transcription factor Jun(JUN),proto-oncogene tyrosine protein kinase Src(SRC)and epidermal growth factor receptor(EGFR).Enrichment analysis showed that the important signaling pathways included PI3K-AKT,AGE-RAGE and MAPK,etc.The results of molecular docking showed that the docking values of core target proteins and active small molecules were all less than-5.0 kcal/mol,which proved that the conclusion was reliable.Conclusion Chonglou Jiedu Formula has multi-target,multi-component and multi-pathway mechanism on wound healing after perianal abscess operation.Among them,special attention should be paid to the active components of Quercetin,Luteolin,Apigenin in Yuxingcao(Houttuyniae Herba),Rutaecarpine in Sanqi(Notoginseng Radix et Rhizoma)and Polyphyllin II in Chonglou(Paridis Rhizoma),the targets of AKT1 and TNF,and signaling pathways of PI3K-AKT,AGE-RAGE,MAPK,etc.The network established in this study helps to recognize the mechanism of Chonglou Jiedu Formula from the molecular level to the pathway level.