基于网络药理学和实验验证研究蓍草解毒利湿功效的作用机制

Mechanism of Action of Achillea alpina L.in Resolving Toxin and Promoting Diuresis Based on Network Pharmacology and Experiment Verification

目的:基于网络药理学与分子对接及体外活性实验探究蓍草解毒利湿功效的作用机制。方法:通过文献查找蓍草的活性成分,使用中药系统药理学数据库与分析平台(TCMSP)筛选蓍草的活性成分,通过TCMSP、GeneCards和比较毒物基因组学数据库(CTD)等数据库检索活性成分作用靶点与疾病作用靶点。将成分作用靶点与疾病作用靶点的共有靶点构建“成分-靶点”网络及蛋白质-蛋白质相互作用(PPI)网络,同时进行基因本体(GO)富集分析及京都基因和基因组百科全书(KEGG)信号通路分析,最后构建“中药-成分-靶点-通路-疾病-功效”网络图,并进行网络拓扑分析筛选出蓍草干预疾病的活性成分和核心靶点,并通过分子对接和体外实验探究活性成分。结果:蓍草发挥传统功效的活性成分26个和相关靶点247个。网络拓扑分析发现,蓍草主要通过作用前列腺素内过氧化物合成酶(PTGS2)、肿瘤坏死因子(TNF)、胱天蛋白酶3(CASP3)、促分裂原活化的蛋白激酶3(MAPK3)等靶点及相关通路发挥功效作用。分子对接结果显示活性成分与PTGS2、TNF、CASP3等核心靶点均能稳定结合。体外活性实验结果显示绿原酸、芒柄花素等成分均具有良好的抗炎活性。结论:本研究基于蓍草“解毒利湿”的传统功效,针对其治疗扁桃体炎、细菌性痢疾、尿道炎展开研究,结果显示蓍草可能通过绿原酸、芒柄花素等成分作用多个靶点和通路干预疾病发生发展过程,为阐释蓍草发挥功效的作用机制提供参考。

Objective:To explore the mechanism of Achillea alpina L.in resolving toxins and promoting diuresis based on network pharmacology,molecular docking,and in vitro activity experiments.Methods:The active ingredients of Achillea alpina L.were found in the literature and screened by using TCMSP.The targets of the active ingredients and the targets of disease were retrieved from the TCMSP,Genecards,and Comparative Toxicogenomics Database(CTD).The common targets of the active ingredients and diseases were constructed as an“ingredient-target”network and protein-protein interaction(PPI)network,and GO enrichment analysis and KEGG signaling pathway analysis were performed to construct the map of“Chinese medicine-ingredient-target-pathway-disease-efficacy”.The network topology analysis was carried out to screen out the active ingredients and core targets of Achillea alpina L.for disease intervention,and the active ingredients were investigated by molecular docking and in vitro experiments.Results:The traditional effects of Achillea alpina L.mainly involve 26 active ingredients and 247 targets.After analyzing the topology of each network,it is found that Achillea alpina L.mainly exerts its effects by acting on targets such as PTGS2,TNF,CASP3,MAPK3,and related pathways.The results of molecular docking show that the active ingredients can stably bind to PTGS2,TNF,CASP3,and other core targets.The results of in vitro activity experiments display that chlorogenic acid,formononetin,and other components exhibit good anti-inflammatory activities.Conclusion:Based on the traditional efficacy of“resolving toxin and promoting diuresis”,the research on the mechanism of Achillea alpina L.in the treatment of tonsillitis,bacterial dysentery,and urethritis is carried out.The results show that Achillea alpina L.may interfere with the development of disease through chlorogenic acid,formononetin,and other components acting on multiple targets and pathways.These results provide a reference for elucidating the mechanism of Achillea alpina L.