Integrated In Vitro, In Vivo, and In Silico Study Reveals Gut‐Protective Effects of Myricitrin From Chinese Bayberry Leaves

ABSTRACT Polyphenols have been widely recognized for their ability to modulate the host inflammatory response and orchestrate the intestinal microenvironment. In this study, epigallocatechin gallate (EGCG), dihydromyricetin‐3′‐O‐sulfate (DMS), and myricitrin were identified as the major bioactive polyphenols in bayberry leaves and subsequently isolated with high purity (≥98%) by preparative liquid chromatography. Among them, myricitrin exhibited strong anti‐inflammatory effects without cytotoxicity in Caco‐2 cells by suppressing NF‐κB activation and downstream inflammatory cytokines. In a DSS‐induced colitis model, myricitrin effectively alleviated disease symptoms, preserved colonic tissue integrity, promoted goblet cell activity, and reduced inflammation‐related cytokines. It also reshaped gut microbiota composition by enriching beneficial genera such as Akkermansia and Ligilactobacillus . Molecular dynamics simulations further revealed stable hydrogen bonding between myricitrin and NF‐κB at key residues, providing mechanistic support for its anti‐inflammatory activity. Together, these findings highlight high‐purity myricitrin as a promising functional food ingredient for intestinal inflammation intervention and microbiota‐targeted modulation.