JiangFuZhiXie pill ameliorates DSS-induced ulcerative colitis in mice by modulating intestinal flora and inhibiting IL6/STAT3 signaling to reduce the inflammatory response

Background Current treatments for ulcerative colitis (UC) are unsatisfactory. JiangFuZhiXie pill (JFZX) is widely used in hospitals as a traditional Chinese medicine for treating UC and has excellent therapeutic effects. Purpose To explore the specific effects and underlying mechanisms of JFZX in the treatment of UC and further search for new therapeutic targets. Methods The UC mouse model was established by providing free access to a 3% dextran sulfate sodium aqueous solution and by intragastric administration of JFZX. Mouse serum was used to measure inflammatory factor levels, including IL-6, IL-1β, and TNF-α. Mouse colon tissues were used for hematoxylin-eosin (H&E), periodic acid-Schiff (PAS), immunohistochemical (IHC), and immunofluorescence (IF) staining. Mouse intestinal contents and colon tissues were used for metagenomic and transcriptomic analyses, respectively. Gene expression was detected using reverse transcription polymerase chain reaction (RT-PCR) and western blot (WB). Results Compared with the DSS group, the JFZX intervention significantly increased body weight and colonic tight junction integrity and decreased disease score, pathological score, and inflammatory levels in UC mice. Metagenomic analysis showed that JFZX modulates the abundance of key bacterial populations and improves intestinal flora disorders in UC mice. Transcriptomic analysis indicated that the key pathway regulated by JFZX in UC treatment is the IL6/STAT3 pathway. RT-PCR, WB, and IF staining showed that JFZX intervention significantly downregulated key targets, including STAT3, IL6, LIF, IL10, IL19, and CSF3, and inhibited STAT3 phosphorylation and nuclear translocation. Conclusion JFZX has ameliorative effects in UC and effectively inhibits intestinal inflammation. Its mechanism of action involves rebalancing the gut microbiota and inhibiting the IL-6/STAT3 signaling pathway, thereby reducing intestinal inflammation-related damage.