Wolfberry Honey and Its Extract Alleviate Dextran Sodium Sulfate‐Induced Ulcerative Colitis by Improving Intestinal Barrier Function and Reducing Oxidative Stress and Inflammation

ABSTRACT Inflammatory bowel disease (IBD) is a chronic condition characterized by gut inflammation causing persistent diarrhea and abdominal pain. Despite the nutritional benefits of wolfberry honey (from Lycium barbarum L.), its potential to alleviate IBD remains underexplored. This study evaluated the protective effects of wolfberry honey and its extract (wolfberry honey extract [WHE]) against dextran sulfate sodium (DSS)‐induced ulcerative colitis (UC) using in vivo and in vitro models. Mice pretreated with wolfberry honey showed significant symptom improvement in DSS‐induced UC, linked to reduced expression of proinflammatory markers (Il‐1β, Il‐6, Tnf‐α, and Mcp‐1) and increased antioxidant genes ( Nrf2 , Sod2 ). Increased Occludin levels indicated improved intestinal barrier function. In vitro, WHE protected DSS‐treated Caco‐2 cells by lowering reactive oxygen species (ROS), stabilizing mitochondrial membrane potential, and inhibiting TLR4/NF‐κB signaling. It enhanced the expression of antioxidant genes and tight junction proteins (ZO‐1, Occludin, and Claudin‐1). Metabolomic analysis revealed that WHE modulated glycerophospholipid metabolism, increasing phosphatidylcholine and choline levels and decreasing lysophosphatidylcholine levels. These results highlight the potential of wolfberry honey and its extract as nutraceuticals for managing UC through their effects on inflammation, oxidative stress, and intestinal barrier function. Further research is warranted to elucidate their mechanisms of action and assess their long‐term therapeutic benefits in IBD management.