基于网络药理学和实验验证探讨二氢杨梅素治疗炎症性肠病的作用机制OACSTPCD

[Objective]To predict and verify the potential target and mechanism of dihydromyricetin(DHM)in the treatment of inflammatory bowel disease(IBD)through network pharmacology and in vitro experiments.[Methods]The targets of dihydromyricetin were obtained from Pubchem database,and the targets of inflammatory bowel disease were obtained from GeneCards,OMIM,TTD,PharmGKB and Drugbank database,and the intersection targets of drug and disease were screened.Build PPI networks with STRING databases and visually screen core targets using Cytoscape.GO function analysis and KEGG path enrichment analysis were performed in R language.The anti-inflammatory effect of dihydromyricetin and its possible mechanism were verified in vitro.[Results]A total of 42 intersecting targets of dihydromyricetin and inflammatory bowel disease were obtained,and 5 core targets F2,NOS3,SHMT1,HCK and DHFR were selected.GO functional analysis and KEGG enrichment analysis showed that dihydromyricetin may play its role through adhesion linkage,chemokines,Ras signaling pathway and so on.RT-PCR showed that dihydromyricetin could inhibit the increase of TNF-α,IL-1[3 and IL-18 mRNA levels which were induced by LPS in HT-29 cells.RT-PCR indicated that the expression levels of NOS3 and HCK mRNA increased after LPS induction,but decreased after DHM intervention.Western Blot analysis showed that dihydromyricetin could effectively restore the LPS-induced downregulation of HT-29 cell connexin.[Conclusion]This study reveals that dihydromyricetin can treat inflammatory bowel disease through multi-pathway and multi-target,and may be effective in the treatment of colitis by restoring intercellular connectivity to improve impaired barrier function.