Preliminary Study On Network Target Prediction And Mechanism Of Yunpi Jiedu Tongluo Qushi Decoction In The Treatment Of Rheumatoid Arthritis

Rheumatoid arthritis(RA)is one of autoimmune diseases with complex pathogeny and pathological mechanism.Inflammatory cell infiltration,pannus formation and the hyperplasia of synoviumthe are the main pathohistological properties of RA,which can eventually lead to cartilage and bone destruction,joint deformity and even physical disability.This seriously affects the quality of life and mental health of patients.Western medicine can alleviate the disease to a certain extent and control the progress of the disease,but there are many adverse reactions.Traditional Chinese medicine decoction has been extensively used in the treatment of RA for thousand years.It has outstanding advantages such as long-lasting efficacy,low toxic side effects and appropriate price.The application of Yunpi Jiedu Tongluo Qushi Decoction in RA can effectively relieve joint symptoms and delay disease progression.However,it's molecular mechanisms remain indeterminate due to the lack of appropriate and scientific research methods.Objective:Using the method of network pharmacology to analyze the composition of Yunpi Jiedu Tongluo Qushi Decoction,predict its active ingredients and corresponding targets,and analyze its potential mechanisms in treating rheumatoid arthritis(RA),so as to provide some guidance for wider application and further revealing its exact molecular mechanism.Method:1.To retrieval and screen the active components and potential targets of each drug in Yunpi Jiedu Tongluo Qushi Decoction by using TCMSP,BATMAN-TCM and TCMID;2.Using GENECARDS,OMIM and DRUGBANK to search and screen targets closely related to RA;3.To select the common targets of all the drugs and RA as the potential targets,and construct the network map of active components,targets and disease through the use of Cytoscape 3.7.2,and to screen the key targets and components by using the network analyzer function;4.To annotate the potential targets with Gene Ontology terms and KEGG pathways by using DAVID6.8 in order to analyze possible biological processes and pathways.Results:1.A total of 161 active ingredients and 282 corresponding targets of Yunpi Jiedu Tongluo Qushi Decoction were obtained through the databases;2.386 targets related to RA were screened thtough GENECARDS,OMIM and DRUGBANK;3.71 common targets of Yunpi Jiedu Tongluo Qushi Decoction and RA were taken as potential targets,and all potential targets and corresponding active components were imported into Cytoscape 3.7.2 for the construction of components-targets-disease network;4.Through network analysis,Seven key targets were selected,which were PTGS2,PPARG,NOS2,PTGS1,MAPK14,RXRA and ACHE;Six key components were obtained,which were quercetin,kaempferol,luteolin,wogonin,formononetin and naringenin;5.By analyzing the enrichment of KEGG pathway,five key pathways with the most significant enrichment were obtained:TNF signaling pathway,NOD-like receptor signaling pathway,Toll-like receptor signaling pathway,T cell receptor signaling pathway and NF-kappa B signaling pathway.Conclusion:1.Quercetin,kaempferol,luteolin,wogonin,formononetin and naringenin which were flavonoids may be the main active ingredients of Yunpi Jiedu Tongluo Qushi Decoction;2.PTGS,PPARG,NOS2,MAPK14 may be the most important targets of Yunpi Jiedu Tongluo Qushi Decoction in the treatment of RA;3.Yunpi Jiedu Tongluo Qushi Decoction may affect TNF signaling pathway,NOD-like receptor signaling pathway,Toll-like receptor signaling pathway,T cell receptor signaling pathway and NF-kappa B signaling pathway to play a therapeutic role in the treatment of RA;4.Yunpi Jiedu Tongluo Qushi Decoction has the characteristics of multi-molecular and multi-target synergistic effect in the treatment of RA,which may play multiple roles in the treatment of RA,such as anti-inflammatory and analgesic,regulating immunity,inhibiting bone destruction,etc.