Abstract
Ulcerative colitis (UC) is characterised by chronic intestinal inflammation and its global prevalence is increasing. Although a variety of drugs have been approved for the clinical treatment of UC, their application is often limited by unsatisfactory long-term effects, side effects, and high treatment costs. Therefore, there is an urgent need for the development of effective drugs with fewer side effects. In this study, we found that the extracellular vesicles extracted and purified from rhizomes of Kaempferia galanga L. (KGEVs) exhibit promising therapeutic effects in treating UC disease. With an average diameter of 133.8 nm, KGEVs are rich in functional components, including lipids, proteins, and pharmacologically and immunologically active molecules. In vivo experiments revealed that KGEVs accumulated in the colorectal region 6 h after oral administration, demonstrating targeted enrichment at the site of enteritis. Moreover, we found that KGEVs effectively alleviate DSS-induced colitis in mice, as indicated by reductions in body weight loss, DAI score, spleen index and colon length shortening. Mechanistically, KGEVs may alleviate colitis by repairing the intestinal barrier, inhibiting oxidative stress and colonic inflammation regulating gut microbiota and inhibiting the polarisation of macrophages into pro-inflammatory M1 macrophages during the inflammatory response, indicating significant anti-inflammatory effects. These results suggest the potential of KGEVs as a promising, cost-effective, and efficient oral therapeutic agents for UC treatment.