基于网络药理学中药复方“三药三方”治疗新冠肺炎的分期治疗分析

Staged Treatment Analysis of the Network Pharmacology Based Traditional Chinese Medicine Compound"Three Chinese Patent Medicines,Three Traditional Chinese Medicine Formula"in the Treatment of COVID-19

目的本研究探究中药复方“三药三方”在新冠肺炎治疗发挥药理作用的多成分、多靶点和多通路的分子机理以及复方药味归经的中医联系,探究“三药三方”药理作用的异同。方法通过ETCM数据库获取“三药三方”的成分、靶点、药味归经,用STRING数据库进行蛋白互作网络构建,用DAVID和Metascape数据库进行靶标功能富集分析,利用Cytoscape软件构建和分析可视化网络图。结果“三药三方”多重点作用于脾经和肺经,初期和中期复方重点作用于肺经和胃经,重症期复方重点作用于肝经和心经,通用方的温性药比例最大,初期和中期复方寒性药比例最大,“三药三方”药味均以苦味、辛味、甘味为主。共同化合物中Alexandrin(胡萝卜甙)与Nsp(N7-MTase)(非结构蛋白C端鸟嘌呤-N7甲基转移酶),Oleanolic Acid(齐墩果酸)与E protein(ion channel)(包膜小膜蛋白)有良好结合力。复方调控共同之处:包含共同子模块γ-氨基丁酸受体亚基相互作用以及细胞色素、ATP依赖转位酶和核受体的相互作用,参与调控16条生物通路涉及①神经保护作用;②免疫调节以及抗炎症风暴调节;③内分泌调节以及性激素调控;④能量代谢调控;⑤药物代谢;⑥其他通路。不同之处:“三药三方”也存在各自特异调控的通路,金花清感颗粒和莲花清瘟胶囊参与ACE2相关通路Renin-angiotensin system(肾素-血管紧张素系统)的调节,同时6种复方有各自的子模块相互作用蛋白。结论“三药三方”在治疗新冠病毒体现辨证论治、治病求因、正气存内、已病防变的中医治疗原则,并且通过网络药理学初步揭示“三药三方”功能调控以及异同之处,阐述“三药三方”通过多成分-多靶点-多通路的综合调控之间的异同关系。

Objective To explored the molecular mechanism of the multi-component,multi-target,and multi-pathway of the pharmacological effects of"Three Chinese Patent Medicines,Three Traditional Chinese Medicine Formula"in the treatment of COVID-19 and the traditional Chinese medicine connection of compounds'medicinal flavor.Methods The ingredients,targets,and flavors of the Chinese herbal compound were obtained through the ETCM database.The STRING database was used to construct the protein interaction network.The DAVID and Metascape databases were used to enrich the target function.The Cytoscape software was used to construct and analyze the visual network diagram.Results"Three Chinese Patent Medicines,Three Traditional Chinese Medicine Formula"mainly focus on the spleen and lung meridians.The mild,common type compound prescriptions mainly focus on the lung and stomach meridians.In the severe stage,the compound prescriptions focus on the liver and heart meridians.In the common type,the proportion of compound cold medicines is the largest."Three Chinese Patent Medicines,Three Traditional Chinese Medicine Formula"mainly include bitter,spicy,and sweet Chinese herb.Among the common compounds,alexandrin and NSP(N7-MTase),Oleanolic Acid and E protein(ion channel)have the good binding ability.The compound regulation has in common:it contains the common sub-moduleγ-aminobutyric acid receptor subunit interaction and the interaction of cytochrome,ATP-dependent transposase,and nuclear receptor,in the regulation of 16 biological pathways involved①neuroprotection role;②immune regulation and anti-inflammatory storm regulation;③endocrine regulation and sex hormone regulation;④energy metabolism regulation;⑤drug metabolism;⑥other pathways.Differences:"Three Chinese Patent Medicines,Three Traditional Chinese Medicine Formula"also have their specific regulatory pathways.Jinhua Qinggan Granule and Lianhua Qingwen Capsule participate in the regulation of ACE2 related pathway Reninangiotensin system,and 6 formulas have their common sub-module interacting proteins,respectively.Conclusion"Three Chinese Patent Medicines,Three Traditional Chinese Medicine Compounds"in the treatment of COVID-19 embodies the principles of TCM treatment based on syndrome differentiation and treatment,the treatment of the disease,righteousness within the qi,and prevention of the disease,and it preliminary reveals the functional regulation and similarities and differences of the Chinese herbal compound through network pharmacology.This study explains the comprehensive regulation of"Three Chinese Patent Medicines,Three Traditional Chinese Medicine Compounds"through multi-component,multi-target,and multi-pathway.