H7F ameliorates DSS-induced colitis through restoration of intestinal barrier function and inhibition of IL-17/NF-κb signaling.

Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the gastrointestinal tract for which effective and safe therapeutic options remain limited. H7F is an in-house herbal formula developed in our hospital based on clinical practice and traditional Chinese medicine theory. This study aimed to investigate the therapeutic effects of H7F on experimental colitis and to explore the underlying mechanisms. Acute colitis was induced in mice by administration of 3% dextran sulfate sodium H7F was orally administered once daily at doses of 100 or 200 mg/kg. Disease severity was evaluated by body weight loss, disease activity index (DAI), colon length, and histopathological changes assessed by hematoxylin and eosin staining. Intestinal barrier function was examined by quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry for ZO-1, occludin, claudin-1, and Muc2. Inflammatory cytokines (Tnf-α, Il-6, Il-10) and apoptosis-related proteins (Bax and Bcl-2) were also analyzed. In addition, gut microbiota composition was assessed by 16S rRNA sequencing, metabolic alterations by untargeted metabolomics, and transcriptomic changes by RNA sequencing. H7F treatment significantly attenuated DSS-induced colitis, as evidenced by reduced body weight loss, lower DAI scores, prevention of colon shortening, and alleviated histopathological injury. Mechanistically, H7F restored intestinal barrier integrity by upregulating tight junction proteins and Muc2 expression, suppressed pro-inflammatory cytokines while enhancing IL10 expression, and reduced colonic epithelial apoptosis by decreasing the Bax/Bcl-2 ratio. H7F also partially reversed gut microbiota dysbiosis, particularly by suppressing pro-inflammatory Peptostreptococcaceae, and corrected metabolic disturbances associated with tyrosine metabolism and ABC transporters. Transcriptomic and molecular analyses further showed that H7F inhibited the IL-17/NF-κB signaling axis, as indicated by reduced IL-17A expression, decreased p65 phosphorylation, and downregulation of Cxcl-1 and Cxcl-2. H7F ameliorated DSS-induced colitis through restoration of intestinal barrier function, modulation of gut microbiota and metabolism, and inhibition of the IL-17/NF-κB signaling pathway. These findings highlight the therapeutic potential of H7F as a multi-target agent for IBD.