ABSTRACT
Objective: To explore the potential action mechanism of Bupleuri Radix and Puerariae Lobatae Radix herb-pair in the treatment of Corona Virus Disease 2019(COVID-19)caused by 2019-nCoV virus through network pharmacology method, so as to provide theoretical guidance for further mechanism and clinical translational research. Method(s): The potential active ingredients and their respective related action targets of Bupleuri Radix and Puerariae Lobatae Radix were obtained through the TCMSP, and the COVID-19-related disease targets were searched by GeneCards database.The common targets from the both screenings were input into the STRING protein interaction online database to construct the interaction network of potential targets.The potential core targets were further screened by MCODE plug-ins.The "ingredients-targets-diseases" network and PPI network were constructed by Cytoscape 3.2.1 software, and GO function enrichment analysis and KEGG signal pathway enrichment analysis were carried out by DAVID v6.8 online software. Result(s): A total of 22 active ingredients and 226 drug targets were screened from Bupleuri Radix and Puerariae Lobatae Radix herb-pair, among which 47 were co-acting targets with COVID-19 and 21 were potential core targets.The results of GO functional enrichment analysis showed that it was mainly related to gene transcriptional expression, inflammatory response and immune system response, while KEGG signal pathway enrichment analysis showed that it was mainly associated with influenza A virus, TNF pathway, Toll-like receptor signal pathway and others. Conclusion(s): Bupleuri Radix and Puerariae Lobatae Radix herb-pair can exert an anti-2019-nCoV effect through its regulatory role in inflammatory reaction and immune system with a multi-ingredients, multi-targets and multi-pathways pharmacological characteristics. Copyright © 2021, Central Station of Chinese Medicinal Materials Information, National Medical Products Administration. All right reserved.
ABSTRACT
Objective: To explore the action mechanism of five Chinese medicines targeting ACE2 for the treatment of COVID-19. Methods: Chinese medicines with human angiotensin converting enzyme II (ACE2) targeting activity were screened through the traditional Chinese medicine (TCM) system pharmacology database and analysis platform (TCMSP), and the TCMSP platform was further utilized to identify the active ingredients of Chinese medicines and their corresponding drug targets. Then, the protein interaction of the above protein targets was analyzed by STRING online database and the relevant data were downloaded. Next, the core sub-network modules in the PPI network system were screened through the MCODE plug-in in CytoScape 3.2.1 software. The functional enrichment analyses of gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) were carried out, using online enrichment analysis software DAVID v6.8, to predict the pharmacological mechanism of the above five Chinese medicines, and to verify and explore the feasibility of compatibility and clinical application of related herb-pair or formula under the theoretical system of TCM. Results: Five Chinese medicines with potential therapeutic effects on ACE2 were selected through the TCMSP platform, namely Bupleuri Radix, Puerariae Lobatae Radix, Puerariae Lobatae Flos, Cyathulae Radix, and Hemerocallis Radix, which contained 42 active ingredients and 240 drug targets. The results of GO biological function enrichment analysis showed that the above five Chinese medicines could affect the biological processes such as inflammatory response, cell apoptosis and proliferation and etc. The results of KEGG pathway enrichment analysis showed that the pharmacological mechanisms of these Chinese medicines were closely related to PI3K-Akt pathway, TNF pathway, FoxO pathway, MAPK pathway, and so on. In TCM theory, Bupleuri Radix and Puerariae Lobatae Radix is a classic herb-pair for the treatment of infectious and febrile diseases. Chaige Jieji Decoction is widely used in febrile diseases in ancient and modern clinics, and has achieved good clinical effects. The main febrile disease treated by this herb-pair is the triple-yang combination of diseases in the syndrome differentiation of the six meridians, which is in line with the syndrome differentiation of TCM in patients with SARS-CoV-2 infection. It can be used with Cyathulae Radix and Hemerocallis Radix in addition and subtraction. Conclusion: The identified five Chinese medicines have multi-target, multi-function and multi-pathway pharmacological effects on the treatment of COVID-19. According to the theoretical analysis of TCM and previous clinical experience, it is suggested that Chaige Jieji Decoction or Bupleuri Radix and Puerariae Lobatae Radix herb-pair can be used to treat COVID-19.