Elucidating therapeutic mechanisms of naringin and phloridzin on ulcerative colitis mice by metabolomics-based comparative analysis.

Naringin and phloridzin are structurally similar flavonoids with anti-inflammatory, antioxidant, and antimicrobial properties, showing considerable potential as natural therapeutic agents. This study demonstrated that naringin and phloridzin exert anti-inflammatory effects and preserve normal intestinal function in UC mice. This protective effect is mediated by inhibition of the NF-κB signalling pathway. To investigate metabolic differences, we employed UPLC-MS/MS-based widely targeted metabolomics alongside targeted analyses of tryptophan (Trp) and short-chain fatty acids (SCFAs). Comparative analysis of metabolic profiles, differential metabolites, and associated pathways revealed regulatory effects on Trp and SCFAs. However, naringin demonstrated superior regulation of Trp metabolism and SCFA levels compared to phloridzin, resulting in more pronounced improvement of gut homeostasis. These findings elucidate the metabolic mechanisms underlying both flavonoid treatments and underscore their potential as complementary therapies for UC.