Citrus pomace extracts preserve intestinal barrier integrity and exhibit antioxidant, antiinflammatory and wound-healing activities in Caco-2 cells

Leaky gut is characterized by increased intestinal permeability due to disrupted tight junctions, allowing harmful molecules to pass through and activate the immune system. Persistent permeability can lead to chronic inflammation, damaging the intestinal wall and contributing to Inflammatory Bowel Diseases (IBD) [ 1 ]. This study, aligned with circular economy principles, investigates the effects of food-grade extracts from orange (OE) and lemon pomace (LE) on lipolysaccaride (LPS)-induced inflammation and wound healing in Caco-2 cells. Phytochemical characterization of OE and LE was conducted via LC-DAD-ESI-MS/MS, followed by HPLC-DAD titration of key compounds: hesperidin and narirutin for OE, hesperidin and eriocitrin for LE. Intestinal bioaccessibility, antioxidant, and anti-inflammatory activities were evaluated through in vitro simulated gastrointestinal digestion and treatment of LPS-stimulated Caco-2 monolayers. The analysis focused on structural proteins related to tight junctions (ZO-1, Claudin-1, Occludin), transepithelial electrical resistance (TEER), reactive oxygen species (ROS) levels, and the expression of antioxidant (CAT, NRF2, SOD2) and inflammatory (IL-1β, IL-6, TNF-α, IL-8) markers. Wound-healing activity was also assessed using hyaluronic acid as a positive control. Both OE and LE digesta demonstrated protective effects against LPS-induced intestinal barrier damage. They effectively reduced oxidative stress, inflammatory responses, and promoted wound healing. In conclusion, although further studies are required to substantiate this hypothesis, including the use of an in vitro co-culture system involving mucus-secreting goblet cells and immune cells, which is currently underway, these findings highlight OE and LE as promising candidates for further preclinical and clinical studies in IBD management. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany