Costunolide and dehydrocostus lactone alleviate ulcerative colitis via regulating TLR4, NF-κB and PI3K expression.

In this study, we aimed to study the mechanism of costunolide (COS) and dehydrocostus lactone (DEH) in the treatment of ulcerative colitis (UC) based on network pharmacology, molecular docking and animal experiments. Firstly, network pharmacology was used to predict the target proteins of compounds and diseases. Subsequently, the network analysis was performed, and the key target proteins were screened out. Finally, molecular docking and animal experiments were conducted to validate the network pharmacology analysis results. A total of 39 common target proteins of compounds and diseases were collected. The target proteins TLR4, PIK3R1, PTGS2, RELA, NOS3, MPO and CHUK were obtained from PPI network analysis, GO analysis, KEGG enrichment analysis, and the compound-target-pathway network. Molecular docking results showed that COS and DEH could bind to these target proteins. The results of animal experiments showed that dextran sulfate sodium (DSS) induced UC in mice, resulting in weight loss, colon shortening, and significantly upregulated expression of TLR4, PIK3R1 and RELA in colon tissue. COS and DEH could reduce these pathological changes in UC mice. And they could alleviate UC by downregulating TLR4, PIK3R1 and RELA. Our findings suggested that COS and DEH could exert protective effects on UC by downregulating TLR4, PIK3R1, and RELA.