Oral administration of Folium Artemisiae Argyi-derived exosome-like nanovesicles can improve ulcerative colitis by regulating intestinal microorganisms

Background: Ulcerative colitis (UC), an inflammatory disease characterized by intestinal barrier dysfunction, poses significant challenges because of the toxicity and adverse effects commonly associated with conventional therapies. Safer and more efficacious treatment strategies are needed. Purpose: The purpose of this study was to treat UC with Folium Artemisiae Argyi exosome-like nanovesicles (FAELNs) and to explore its related mechanism to provide a safer and more effective means for the treatment of ulcerative colitis. Methods: We established an in vivo model of acute UC in mice and an in vitro inflammatory model using HT-29 human colorectal cancer cells. To evaluate the therapeutic effect of FAELNs on UC, we adopted various proxies, including changes in body weight and disease activity index (DAI) of mice, and measurement of colon length. The concentrations of myeloperoxide, interleukin (IL-1 beta), IL-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and interferon-gamma in sera of mice were detected by ELISA. Immunohistochemistry, hematoxylin and eosin staining, and Alyssin blue staining were performed. The effect of HT-29 cells on oxidative stress was detected using an active oxygen probe, diacetyldichlorofluorescein, and flow cytometry. Western blotting was performed to detect the expression levels of Bax and Bcl-2 in HT-29 cells treated with FAELNs. The effects of FAELNs on IL-6 and IL-1 beta were detected by fluorescence quantitative PCR. Fecal 16S bacteria were detected, and the role of FAELNs was verified by alpha diversity and beta diversity analyses, principal component analysis, species distribution, and function prediction. For microRNA sequencing of FAELNs, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed. To detect the metabolic and lipid groups of FAELNs, the components were identified and a pharmacological network was constructed to explore the related mechanisms and diseases.