关键词: 硫代葡萄糖苷, 炎症性肠病, 结球甘蓝, 分子对接

Abstract:

The purpose of this paper is to explore the mechanism of action of glucosinolates (GSL) in common head cabbage for the treatment of inflammatory bowel disease (IBD).Using public databases,this study obtained the targets of IBD and GSL,took the intersection of the two,constructed the protein interactions network,and analyzed their potential targets for the treatment of IBD using GO and KEGG enrichment.The binding energy between glucobrassicin (GBC),the active monomer component of GSL,and the core target was verified by molecular docking.Mice models of IBD were established with dextran sodium sulfate,and their disease activity index scores,intestinal permeabilities,intestinal tissue tumor necrosis factor-α (TNF-α) and other cytokine levels were detected.The proliferative activity of human colorectal adenocarcinoma cells was detected using a kit,and the levels of TNF-α and interleukin-1 (IL-10) released from this cell induced by lipopolysaccharide (LPS) were detected by ELISA.Ninety-two intersection targets of IBD and GSL were obtained.GO functional analysis indicated that various biological processes,such as regulation of inflammatory response and modulation of kinase activity,were involved in the developmental process of IBD.Ten targets for the treatment of IBD by GSL,such as topoisomerase Ⅱα (TOP2A),cell cycle protein-dependent kinase 1 (CDK1),cytochrome P4502C9 (CYP2C19) were obtained;In the KEGG enrichment analysis,the pathways with higher relevance included the TRP channel inflammatory mediator-regulated pathway.Molecular docking showed that GBC had better binding activity with the core targets.The medium and high GSL groups slowed down the weight loss and improved the condition of mice,such as loose stool and blood in stool,and significantly reduced the DAI score of the model group (P<0.001),lowered the levels of cytokines,such as TNF-α,in the intestinal tissues of the mice (P<0.001),and elevated the levels of IL-10 (P<0.001).In the concentration range of 20-300 μmol/L,GSL promoted the proliferation of human colorectal adenocarcinoma cells,inhibited LPS-induced TNF-α secretion,and elevated IL-10 levels.The above results suggested that GSL could attenuate the inflammatory response of the mouse intestine and alleviate the symptoms of inflammatory bowel disease by inhibiting TOP2A and CDK1 protein expression.

Key words:

glucosinolate, inflammatory bowel disease, common head cabbage, molecular docking