Ulcerative colitis (UC) is a chronic inflammatory condition with recurrent and challenging symptoms. Effective treatments are lacking, making UC management a critical research area. Morin (MO), a flavonoid from the Moraceae family, shows potential as an anti-UC agent, but its mechanisms are not fully understood. Using a dextran sulfate sodium (DSS)-induced UC mouse model, we employed network pharmacology to predict MO's therapeutic effects. Assessments included changes in body weight, disease activity index (DAI), and colon length. Immunofluorescence, hematoxylin and eosin (H&E), and PAS staining evaluated colon damage. ELISA and western blot analyzed inflammatory factors, tight junction (TJ)-associated proteins (Claudin-3, Occludin, ZO-1), and Mitogen-Activated Protein Kinase (MAPK)/ Nuclear Factor kappa B (NF-κB) pathways. 16S rRNA sequencing assessed gut microbiota diversity, confirmed by MO's modulation via Fecal Microbial Transplantation (FMT). Early MO intervention reduced UC severity by improving weight, DAI scores, and colon length, increasing goblet cells, enhancing barrier function, and inhibiting MAPK/NF-κB pathways. MO enriched gut microbiota, favoring beneficial bacteria like Muribaculaceae and Erysipelotrichaceae while reducing harmful Erysipelotrichaceae and Muribaculaceae. This study highlights MO's potential in UC management through inflammation control, mucosal integrity maintenance, and gut flora modulation.

Intestinal epithelial immune dysfunction or imbalance in the homeostasis of intestinal flora can lead to the occurrence or exacerbation of ulcerative colitis (UC). Prim-O-glucosylcimifugin (POG) is an extract of Chinese traditional medicine (TCM) Saposhnikov, which has analgesic, anti-inflammatory, and antioxidant effects. The present work discussed how the POG alternated ulcerative colitis (UC) along with its underlying mechanism. This was clarified by performing animal studies in a mice model, wherein UC was induced by dextran sulfate sodium (DSS). In vivo studies have found that POG increased clinical score, colonic length, and weight of mice in the ulcerative colitis model. It repaired the pathological injury of an intestinal mucosa within mice while inhibiting the inflammatory factor levels such as IL-1β, TNF-α, and IL-6. Meanwhile, by16SrDNA sequencing analysis, it was found that POG regulated the richness of intestinal microbiota structure and repaired the intestinal immune barrier by upregulating the expression levels of tight junction proteins Occludin, Claudin-3, and ZO-1. To further confirm the above results, we found in in vitro studies that POG also protected lipopolysaccharide- (LPS-) induced RAW264.7 cells. POG dramatically suppressed inflammatory factor production (including TNF-α, IL-1β, and IL-6) within LPS-treated RAW264.7 cells by inhibiting the activation of ERK1/2, AKT, JNK1/2, IκB-α, P38, and P65 phosphorylation. In conclusion, POG plays a protective role against UC by inhibiting the activation of pro-inflammatory signaling pathways MAPK, AKT, and NF-κB; repairing the integrity of the intestinal barrier; and regulating the diversity and abundance of intestinal flora.

Camptothecin (CPT) is a cytotoxic quinoline alkaloid isolated from the bark and branches of the Chinese tree Camptotheca acuminata. CPT inhibits topoisomerase I. It possesses various antitumor activities and is mainly used in the treatment of colon, ovarian, liver, and bone cancers as well as leukemia. CPT inhibits the expressions of inflammatory genes and can prevent death from chronic inflammation. Therefore, we investigated the effect of CPT treatment in ulcerative colitis (UC) using DSS-induced UC mouse model; after that, we explored its potential mechanisms. Here, we found that CPT exerted protection on DSS-induced UC in rats. In addition, the administration prominently reduced the disease activity index as well as colon length of the model rats and remarkably reduced the inflammatory cytokines. Further, CPT significantly reduced several vital proinflammatory proteins in LPS-induced RAW264.7 cells. In summary, our findings demonstrate that CPT is hopefully to act as a therapeutic agent for UC.