Fufang Tongye Shaoshang You repairs ulcerative colitis in mice caused by DSS based on the balanced strategy of "inflammation inhibition-microbiota regulation-mucosa protection".

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a complex inflammatory bowel disorder characterized by immune dysregulation, intestinal barrier dysfunction, and intestinal microbiota imbalance. Current therapies remain limited, highlighting the need for alternative strategies. Fufang Tongye Shaoshang You (TYY), a traditional ethnomedicine historically used for diarrhea and ulcers, exhibits promising therapeutic potential against UC. AIM OF THE STUDY: This study aims to evaluate the therapeutic efficacy of TYY in UC mice and to systematically elucidate its underlying mechanisms and potential bioactive constituents. MATERIALS AND METHODS: A dextran sulfate sodium (DSS)-induced UC mouse model was established to evaluate the reparative effect of TYY by assessing disease activity, colon length, and histopathology. Systemic effects were examined through spleen index and serum markers of liver and kidney function. Key UC-associated targets were identified via analysis of GEO transcriptomic datasets. The anti-inflammatory and barrier-protective mechanisms of TYY were explored using a series of molecular and histological techniques. Intestinal microbiota changes were analyzed with 16S rRNA gene sequencing. Furthermore, serum pharmacochemistry (UPLC-Q-TOF-MS) identified and prioritized circulating components, which were validated in a lipopolysaccharide (LPS)-stimulated Caco-2 cell model for their regulatory effects in vitro. RESULTS: TYY exerted comprehensive therapeutic effects on UC by inhibiting IL-17 signaling pathway, rebalancing intestinal microbiota, and protecting intestinal mucosa, while also improving DSS-induced liver, kidney, and spleen dysfunction. Seven key bioactive components were identified as the primary pharmacodynamic substances responsible for TYY's efficacy. CONCLUSIONS: This work systematically elucidates the multi-target mechanism of TYY in treating UC, demonstrating that its therapeutic efficacy arises from a balanced strategy encompassing inflammation inhibition, microbiota regulation, and mucosa protection-showing demonstrable superiority over its vehicle alone and being friendly to extra-intestinal organs. The identification of seven bioactive components and their differential targeting of the IL-17 signaling network provides a mechanistic foundation for repurposing this topical ethnomedicine as a promising oral complementary therapy for UC.