基于网络药理学探讨藿朴夏苓汤“培土生金”治疗新型冠状病毒肺炎的潜在作用机制

Study on the Potential Mechanism of Huopuxialing Decoction and its "Peitushengjin" Theory in the Treatment of COVID-19 Based on Network Pharmacology

目的:采用网络药理学探索藿朴夏苓汤治疗新型冠状病毒肺炎(COVID-19)的作用机制。方法 :首先从《雷公炮制药性解》《本草汇言》《中药大辞典》等书中对藿朴夏苓汤的药物归经规律进行挖掘。其次,运用中药系统药理学数据库与分析(TCMSP)平台检索该复方各味药的有效成分和作用靶点。并将经过Uniprot数据库检索的靶基因及TCMSP检索出的相应中药成分、中药名称输入Cyoscape3.7.1软件,使"药物-有效成分-靶点"网络可视化。然后运用GeneCards平台筛选疾病基因,并将该基因与药物靶蛋白取交集,通过STRING平台对交集靶点的相互作用关系进行探索,找寻藿朴夏苓汤治疗COVID-19的关键靶点,通过Cyoscape3.7.1软件构建PPI网络图。最后进行GO功能富集分析和KEGG通路富集分析,预测其作用机制及核心靶标,并绘制气泡图及柱状图以使结果可视化。结果:藿朴夏苓汤各药的归经以肺、脾、胃为主,并涉及心、肝、肾、三焦、大肠、小肠、膀胱等多个脏腑;"药物-有效成分-靶点"网络涉及10味中药、68个有效药物成分,217个靶基因;将药物基因与疾病基因取交集,根据基因相互作用关系获取65个关键基因。按照P<0.05的标准,GO富集到1 739条生物过程,39条细胞组成,110条分子过程,KEGG富集到PI3K-Akt信号通路、小细胞肺癌、乙型肝炎等与之密切相关的136条信号通路。结论:本文预测具有"培土生金"多脏腑治疗作用的藿朴夏苓汤,其主要化合物成分槲皮素、木犀草素、黄芩素等可能通过作用AKT1、MAPK1、RELA、CDKN1A、CCND1、CASP8等关键靶点调节多条信号通路,从而发挥对COVID-19的治疗作用。

Objective: To explore the mechanism of Huopuxialing Decoction in the treatment of COVID-19 pneumonia. Methods: First of all, the principle of drug meridian tropism of Huopuxialing Decoction was excavated from the books: Processing solution of Leigongteng, Bencaohuiyan and Dictionary of traditional Chinese medicine. Then, TCMSP platform was used to search the effective components and targets of the compound. The target genes retrieved by UniProt database and the corresponding components and names of traditional Chinese medicine retrieved by TCMSP were input into Cyoscape 3.7.1 software to visualize the network of "drug-effective component-target". Then we use Genecards platform to screen the disease gene, and take the intersection of the gene and the drug target protein, then we explore the interaction relationship of the intersection target by string platform, to find the key target of Huopuxialing Decoction in the treatment of new coronary pneumonia, also the Cyoscape 3.7.1 software was used to build PPI network diagram. Finally, through the analysis of GO function enrichment and KEGG pathway enrichment, the mechanism of action and the core target are predicted, and the bubble chart and histogram are drawn to visualize the results. Results: The main meridian tropism of Huopuxialing decoction was Fei, Pi and Wei system, also involving Xin, Gan, Shen, Sanjiao, large intestine, small intestine, bladder and many other viscera. The "drug-effective component-target" network involved 10 traditional Chinese medicines, 68 effective drug components and 217 target genes. Drug-based factors and disease genes were intersected, and 65 key genes were obtained according to the gene interaction relationship. According to the P<0.05 standard, 1739 biological processes, 39 cell components and 110 molecular processes were enriched by GO analysis, PI3 K Akt signal pathway, small cell lung cancer, hepatitis B and other related 136 signal pathways were enriched in KEGG. Conclusion: In the study of "Peitushengjin" theory, the main compounds of Huopuxialing decoction are quercetin, luteolin and baicalein, which may treat on COVID-19 pneumonia by regulating multiple signal pathways through key targets such as AKT1、MAPK1、RELA、CDKN1 A、CCND1 and CASP8.