Study On The Mechanism Of Tongfengding Capsule In The Treatment Of Gout And Hyperuricemia Based On Network Pharmacology

Obiective:This study is based on a network pharmacological approach to investigate the active ingredients and pharmacological mechanisms of action of Tongfengding capsules in the treatment of gout and hyperuricemia,to providing a theoretical reference for the clinical use of Tongfengding capsules in the treatment of gout and hyperuricemia,as well as a reference for clinical pharmacological studies on Chinese medicine.Methods:The TCMSP database was used to obtain the active ingredients and targets of Gentiana macrophylla,Cortex phellodendri,Rhizoma corydalis,Radix paeoniae rubra,Radix cyathulae,Alisma,Semen plantaginis,Glabrous greenbrier rhizome,and for those compounds for which no target was retrieved,the active ingredients were obtained from the PubChem database or the 2D structures of the compounds were drawn by ChemDraw17.1 software.Then,the SwissTarget Prediction platform was used to predict the relevant protein targets,and the GeneCards database,OMIM database,TTD database,DisGeNET database,DigSee database and DrugBank database were used to search for targets related to gout and hyperuricemia diseases,and standardised specification of the screened protein targets using the Uniprot protein database.Building a PPI network of intersecting targets using the String online platform.By using Cytoscape 3.8.0 visualization software,we performed topological analysis of the network and screened the core targets,constructed the "active ingredient-target" network and constructed the "active ingredient-gout and hyperuricemia disease-target-pathway" network,to identify the active ingredients and protein targets for the treatment of gout and hyperuricaemia in Tongfengding capsules.Use of the Metascape platform to perform GO functional enrichment analysis and KEGG biological pathway enrichment analysis on the core targets can lead to the possible mechanism of action of gout and hyperuricemia treatment with Tongfengding capsules.Finally,we performed molecular docking with Autodock vina software to verify the reliability and tightness of binding of key component compounds to the core targets.Results:By searching the TCMSP database and the predicted targets,a total of 132 active ingredient compounds and 659 action targets were obtained for gout and hyperuricemia capsules,as well as a total of 1715 disease targets for gout and hyperuricemia by searching six major disease databases.The main components include quercetin,zedoary alcohol B,zedoary alcohol C,cyproterone,canthaxanthin A and palm rhubarb dianthrone B.Also,the key targets of action are PTGS2,PGTS1,SCN5 A,HSP90 and KCNH2.Multiple signaling pathways,including cancer pathways,AGE-RAGE signaling pathway of diabetes complications,Kaposi’s sarcoma-associated herpes virus infection,and IL-17 signaling pathway,play a role in the treatment of gout and hyperuricemia.The molecular docking showed stable and reliable binding of quercetin,zeranol B and zeranol C in comparison with aspirin ibuprofen.Conclusion:Tongfengding capsules for the treatment of gout and hyperuricemia due to the antiinflammatory effect of quercetin,the main component,acting on prostaglandin G/H synthase via the IL-17 pathway.It also provides preliminary evidence of the multicomponent,multi-target and multi-pathway characteristics of gout and hyperuricemia treatment with Tongfengding capsules.This study systematically analyzed the active ingredients,protein targets and biological pathways of gout and hyperuricemia in the treatment of gout and hyperuricemia with Tongfengding capsules based on a network pharmacology research method,and provided a pharmacological basis for the clinical use of Tongfengding capsules in the treatment of gout and hyperuricemia.