The Medicine and Food Homologous formula alleviates DSS-induced colitis in mice by regulating the IL-17A/CEBPβ/inflammatory factor axis

Medicinal herbs sharing origins with both medicine and food possess rich pharmacological and nutritional properties, forming a vital interdisciplinary nexus that bridges medical science, pharmacology, and culinary arts. The therapeutic landscape of Medicine and Food Homologous Formula (MFHF) for ulcerative colitis (UC) remains underexplored, urgently demanding systematic investigation to develop safer, more potent prescriptions and unravel their intricate mechanisms. Leveraging reverse network pharmacology, we identified top-ranked medicine and food homologous herbs to construct a core MFHF with demonstrated efficacy against DSS-induced UC, administered orally. RNA sequencing (RNA-seq) revealed differentially expressed genes in colonic tissues, while rigorous qRT-PCR validation pinpointed critical regulatory genes. Biological pathway analysis further uncovered the MFHF's multi-target therapeutic actions mediated through key signaling cascades. The MFHF, comprising six homologous herbs, jujube, sea buckthorn, licorice, sophora flower, puerca, and lotus leaf, effectively alleviated UC symptoms and colon damage in mice, primarily modulated the IL-17A signaling pathway, dramatically suppressing the expression of IL-17A, Act1, and CEBPβ. This modulation consequently reduced the expression of key downstream inflammatory factors. The involvement of IL-17A/CEBPβ pathway genes was further confirmed by qRT-PCR and Western Blot. Our findings demonstrate that MFHF significantly mitigates DSS-induced colon inflammation in mouse models by modulating the IL-17A/CEBPβ signaling axis, thereby curtailing the excessive release of inflammatory mediators. • A novel Medicine and Food Homologous Formula (MFHF) was constructed based on reverse network pharmacology, featuring both safety and nutritional activity. • MFHF targeted regulation of the IL-17A/CEBPβ/inflammation signaling axis. • In vitro and in vivo experiments confirmed that MFHF alleviates the inflammation in cells and DSS-induced mice. • Combined with UPLC-Q-TOF-MS and RNA-seq, core compounds were identified, providing a novel natural dietary intervention in UC.