Quercetin, a flavonoid that is present in vegetables and fruits, has been found to have anti-inflammatory effects. However, the mechanism by which it inhibits colitis is uncertain. This study aimed to explore the effect and pharmacological mechanism of quercetin on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC). Mice were given a 4% (w/v) DSS solution to drink for 7 days, followed by regular water for the following 5 days. Pharmacological mechanisms were predicted by network pharmacology. High-throughput 16S rDNA sequencing was performed to detect changes in the intestinal microbiota composition. Enzyme-linked immunosorbent assay and western blotting were performed to examine the anti-inflammatory role of quercetin in the colon. Quercetin attenuated DSS-induced body weight loss, colon length shortening, and pathological damage to the colon. Quercetin administration modulated the composition of the intestinal microbiota in DSS-induced mice and inhibited the growth of harmful bacteria. Network pharmacology revealed that quercetin target genes were enriched in inflammatory and neoplastic processes. Quercetin dramatically inhibited the expression of phosphorylated protein kinase B (AKT) and phosphatidylinositol 3-kinase (PI3K). Quercetin has a role in the treatment of UC, with pharmacological mechanisms that involve regulation of the intestinal microbiota, re-establishment of healthy microbiomes that favor mucosal healing, and the inhibition of PI3K/AKT signaling.

Hordenine, a phenethylamine alkaloid, is found in a variety of plants and exhibits a broad array of biological activities and pharmacological properties, including anti-inflammatory and anti-fibrotic effects. However, the efficacy and underlying mechanisms of hordenine in treating ulcerative colitis (UC) remain unclear. To address this, we examined the therapeutic effects of hordenine on dextran sodium sulphate (DSS)-induced UC by comparing disease activity index (DAI), colon length, secretion of inflammatory factors, and degree of colonic histological lesions across diseased mice that were and were not treated with hordenine. We found that hordenine significantly reduced DAI and levels of pro-inflammatory factors, including interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α), and also alleviated colon tissue oedema, colonic lesions, inflammatory cells infiltration and decreased the number of goblet cells. Moreover, in vitro experiments showed that hordenine protected intestinal epithelial barrier function by increasing the expression of tight junction proteins including ZO-1 and occludin, while also promoting the healing of intestinal mucosa. Using immunohistochemistry and western blotting, we demonstrated that hordenine reduced the expression of sphingosine kinase 1 (SPHK1), sphingosine-1-phosphate receptor 1 (S1PR1), and ras-related C3 botulinum toxin substrate 1 (Rac1), and it inhibited the expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in colon tissues. Thus, hordenine appears to be effective in UC treatment owing to pharmacological mechanisms that favor mucosal healing and the inhibition of SPHK-1/S1PR1/STAT3 signaling.