Phenolic compounds from Lindera aggregata (Sims) Kosterm. ( L. aggregata ) leaves and their effects on colitis: A preliminary study

BACKGROUND: Developing active ingredients derived from natural plants for the intervention of ulcerative colitis (UC) is an effective strategy to replace conventional drugs with severe side effects. Lindera aggregata (Sims) Kosterm. (L. aggregata) leaves are an edible and medicinal herb with significant commercial value. However, the phenolics of these leaves and their effects in alleviating colitis remain unknown. OBJECTIVE: Analysis of polyphenolic components from L. aggregata leaves and their mechanism of action in improving colitis. METHODS: In this study, the phenolic composition and digestive properties of the methanol extract derived from L. aggregata leaves (LLME) were characterized using UPLC-QTOF-MS combined with an in vitro digestion model. Subsequently, a dextran sulfate sodium (DSS)-induced colitis model in mice was employed to evaluate its anti-inflammatory mechanism. RESULTS: Forty phenolic components were tentatively identified from the LLME, mainly including kaempferol, quercetin and their glycosides. These compounds exhibited different digestive fates in the gastrointestinal tract, and might reach the colon. In vivo experiments demonstrated that LLME treatment effectively ameliorated weight loss and colon shortening, upregulated the expression of tight junction (TJ) protein, and suppressed the TLR4/MyD88/NF-κB and MAPK pathways, thereby inhibiting the production of downstream inflammatory mediators. Additionally, LLME regulated the intestinal microbiota and elevated short-chain fatty acids (SCFAs) level. CONCLUSION: Our findings suggest that LLME exerts a comprehensive protective effect on intestinal inflammation through multi-target regulation. This work offers a potential natural candidate for further preclinical and clinical evaluation in UC management, and provides a foundation for the application of L. aggregata leaves as functional food resources. HIGHLIGHTS: This work systematically characterized the polyphenols and their in vitro digestive characteristics of L. aggregata leaves, and firstly elucidated their action mechanisms in alleviating colitis.