Mechanism of action of resveratrol in treatment of rheumatoid arthritis through network pharmacology and experimental validation
Objective To explore the therapeutic effects and potential mechanisms of resveratrol in rheumatoid arthritis through network pharmacology,molecular dynamics simulations and animal experiments,and experimental verification was carried out.Methods The TCMSP,Batman-TCM,and SwissTargetPrediction databases were used to predict the targets of action of resveratrol.GeneCards and OMIM databases were used to predict the potential therapeutic targets of rheumatoid arthritis.PPI networks were constructed using STRING and Cytoscape 3.8.0,and MCC analysis,MCODE analysis,GO and KEGG enrichment analysis,and target network mapping between KEGG pathways and targets were performed.Using molecular docking and molecular dynamics simulation methods to simulate the core targets with resveratrol.Constructing a rheumatoid arthritis rat model,and detecting the expression levels of p-PI3K,p-Akt,and p-ERK1/2 by Western blotting.Results A total of 310 targets of resveratrol and 207 intersecting targets with rheumatoid arthritis.MCC analysis found that Akt1,PIK3CA,PIK3CB,MAPK1,MAPK3,and STAT3 are the core genes among them.GO and KEGG enrichment analysis found that pathways in cancer,AGE-RAGE signaling pathways in cancer,apoptosis,PI3K-Akt signaling pathway may be the key pathways of resveratrol affecting rheumatoid arthritis.Molecular docking and molecular dynamics simulation also found that Akt1,PIK3CA,and MAPK1 have strong binding ability with resveratrol.Animal experiments revealed that compared with the control group,the arthritis index of the model group was significantly increased,but the arthritis index in the resveratrol group was significantly decreased.The expression of p-PI3K and p-Akt was significantly increased,while the expression of p-ERK1/2 was significantly decreased(P<0.05,0.01).Conclusion Resveratrol can improve arthritis index of rheumatoid arthritis rats,and may play a key therapeutic role through the targets of Akt1,PIK3CA,and MAPK1 and the PI3K/Akt signaling pathway.
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