基于中药药性理论探索“性味网络药理学”的合理性与可行性——以如金解毒散干预病毒性肺炎的性味网络药理学研究为例

Exploring the rationality and feasibility of “property and flavor network pharmacology” based on the theory of property and flavor of Chinese medicine: Taking the property and flavor network pharmacology of Rujin Jiedu Powder in treating viral pneumonia

目的:基于中药药性理论,首次提出"性味网络药理学"概念,通过构建中药性味网络并结合分子对接技术,探索经典方剂如金解毒散治疗病毒性肺炎的作用机制。方法:从HERB数据库获取如金解毒散主要成分,GeneCards收集病毒性肺炎相关基因,借助NetInfer和BATMAN-TCM数据库构建如金解毒散性味药物模块的成分-靶点-疾病模型相互关系网络。采用Metascape软件对靶点进行蛋白相互作用网络和KEGG分析;采用Vina软件对成分和靶蛋白进行分子对接验证;采用SwissADME软件进行有效成分药物代谢动力学评价。结果:利用中药数据库共筛选出该方有效成分335个,其中桔梗20个,甘草117个,黄连26个,黄芩62个,黄柏75个,山栀35个。按3种性味模块进行靶点预测及网络构建,其中苦辛平模块(桔梗)潜在靶标596个,甘平模块(甘草)潜在靶标819个,苦寒模块(黄连、黄芩、黄柏、山栀)潜在靶标1 097个。网络分析及分子对接结果显示,异甘草黄素、穿贝海绵甾醇、吴茱萸次碱、草香豆酮、黄芩素、槲皮素、木犀草素等是该方治疗病毒性肺炎的重要活性成分;SRC、FYN、LCK、MET、AKT1、ABL1、MAPK8、ITK、CCR5、TP53、PTPN11、EIF2AK2、MAPK1、PIK3CD、MAPK3、BTK、STAT3、PIK3CA、MAPK14等是该方治疗病毒性肺炎的核心靶蛋白;JAK-STAT信号通路、细胞因子-细胞因子受体相互作用等是该方治疗病毒性肺炎的关键信号通路。结论:本研究通过性味网络药理学及分子对接技术揭示了如金解毒散多组分、多靶点、多通路的特点,为进一步探索如金解毒散治疗病毒性肺炎作用机制提供了新的思路与方法。研究也表明,采用性味药物模块成分-靶点-疾病模型探析中药复方物质基础具有一定的合理性与可行性。

Objective: Based on the theory of property and flavor of Chinese medicine, the concept of “property and flavor network pharmacology” is proposed for the first time. The aim is to explore the mechanism of classical prescriptions Rujin Jiedu Powder in the treatment of viral pneumonia by constructing property and flavor network of Chinese medicine combined with molecular docking technology. Methods: The main components of Rujin Jiedu Powder were obtained from HERB database, and viral pneumonia related genes were collected by GeneCards. NetInfer and BATMAN-TCM databases were used to construct the relationship network of property and flavor module component-target-disease model for Rujin Jiedu Powder. The protein-protein interaction network and KEGG analysis for targets were performed by Metascape software. Molecular docking verification of components and target proteins were performed by Vina software. The pharmacokinetics of the active components was evaluated by SwissADME software. Results: A total of 335 active components of this prescription were screened out using Chinese medicine databases, among 20 components from Platycodonis Radix, 117 components from Glycyrrhizae Radix et Rhizoma, 26 components from Coptidis Rhizoma, 62 components from Scutellariae Radix, 75 components from Phellodendri Chinensis Cortex and 35 components from Gardenia Fructus. Target prediction and network construction were carried out according to three kinds of property-flavor modules, and there were 596 potential targets in bitter-pungent-calm module(Platycodonis Radix), 819 potential targets in sweet-calm module(Glycyrrhizae Radix et Rhizoma) and 1 097 potential targets in bitter-cold module(Coptidis Rhizoma, Scutellariae Radix, Phellodendri Chinensis Cortex, Gardenia Fructus). Network analysis and molecular docking results showed the important active components(Isolicoflavonol, Clionasterol, Rutaecarpine, Licocoumarone, Baicalein, Quercetin and Luteolin), core target proteins(SRC, FYN, LCK, MET, AKT1, ABL1, MAPK8, ITK, CCR5, TP53, PTPN11, EIF2 AK2, MAPK1, PIK3 CD, MAPK3, BTK, STAT3, PIK3 CA, MAPK14) and key signal pathways(JAK-STAT signaling pathway, cytokine-cytokine receptor interaction) of Rujin Jiedu Powder in the treatment of viral pneumonia. Conclusion: In this study, the property and flavor network pharmacology and molecular docking are used to reveal the characteristics of multi-components, multi-targets and multi-pathways of Rujin Jiedu Powder, which provides new idea and method for further studying the mechanism of Rujin Jiedu Powder in the treatment of viral pneumonia. Research also shows that, it is reasonable and feasible to explore the material basis of Chinese medicine compound recipes by property and flavor module component-target-disease model.