Perspective of Dimethyl Fumarate for Diverse Immune Diseases Treatment and Involvement in Mechanisms Based on Network Pharmacology
OBJECTIVE To explore the potential application and underlying mechanisms of dimethyl fumarate(DMF),a first-line drug for multiple sclerosis(MS),in the treatment of various autoimmune diseases using network pharmacology.METHODS 2D and 3D structures of DMF as well as Canonical SMILES were retrieved by Pub-chem,the target was predicted in the Targetnet database,and the duplicated target was removed and normalized by Uniprot(protein database).GeneCards,OMIM and TTD databases were used to summarize different immune disease targets.Venny online acquisition of DMF targets and different immune disease target intersection genes.The intersec-tion gene was combined with the STRING database and Cytoscape 3.8.2 software to construct a PPI network to obtain the core target.DAVID database was used for GO and KEGG enrichment analysis of intersection genes.Cytoscape 3.8.2 software was used to construct the"drug-disease-target-pathway"Network diagram,and Network Analysis was conducted to analyze the correlation and importance of each factor(node)in the diagram.AutoDock vina software was used to conduct molecular docking between core components and core targets respectively,and Pymol software visualized the docking results.RESULTS The potential targets of DMF were identified as 216,with 19 key targets being used to treat various immune-related diseases,including psoriasis,rheumatoid arthritis,colitis,multiple sclero-sis,systemic sclerosis,and systemic lupus erythematosus.The important targets include MMP9,PTGS2,and TNF.GO enrichment analysis showed that DMF had an impact on cell molecular function,biological function,and cell composi-tion.KEGG results showed that DMF regulation of these functions was mainly related to the PI3K/AKT,TNF,NF-κB,and IL-17 signaling pathways.Molecular docking results showed that DMF had binding activity with the core tar-gets.CONCLUSION This study discovered that DMF can intervene in the development of various immune-related diseases at both cellular and molecular levels through multiple targets and pathways.As a first-line drug for MS,DMF has the potential to treat other autoimmune diseases,which is of great significance.
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