Rosa roxburghii ‐Derived Exosome‐Like Nanovesicles Alleviate Ulcerative Colitis Based on Th17/Treg Immune Balance and Gut Microbiota Modulation

ABSTRACT Plant‐derived nanovesicles (PDVs), an innovative and bioactive form of natural products, are key mediators of intercellular communication, as they can deliver bioactive payloads to target cells. As a traditional functional food, Rosa roxburghii ‐derived exosome‐like nanovesicles (RNVs) have not been fully characterized in colitis pathogenesis. This study investigated the efficacy of RNVs in a murine colitis model via dextran sulfate sodium (DSS) salt exposure. RNVs have a nanoscale size (< 200 nm hydrodynamic diameter) and favorable colloidal stability. In vitro experiments using primary human macrophages demonstrated the superior biocompatibility of RNVs. RNV pre‐administration alleviated pathological features in murine DSS‐colitis, which was confirmed by in vivo experiments. This study provides solid evidence that RNVs ameliorate DSS‐induced colitis in murine models through multipronged mechanisms: (i) reconstitution of gut microbiota composition; (ii) elevating levels of short‐chain fatty acids; (iii) modulating inflammatory mediators and antioxidant factors and restoring intestinal barrier integrity via tight junction regulation; and (iv) rebalancing of Th17/Treg immune responses. In conclusion, this study reveals the essential pathways responsible for the anti‐inflammatory/antioxidant actions of PDVs and demonstrates their translational potential as novel nanovesicle‐based carriers for functional foods.