Zanthoxylum bungeanum-Derived Nanobiotics for Effective Against Ulcerative Colitis in Mouse Model

Qianyuan Gong,1 Caiyun Sun,2 Tao Jiang,3 Yuanbiao Guo1 1Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, 610031, People’s Republic of China; 2College of Animal Science, Xichang University, Xichang, 615013, People’s Republic of China; 3School of Laboratory Medicine, North Sichuan Medical College, Nanchong, 637100, People’s Republic of ChinaCorrespondence: Qianyuan Gong, Email [email protected]: Growing research is devoted to the development of plant-derived products as new therapeutic drugs to reduce side effects. Plant-derived exosome-like nanoparticles (ELNs) have shown promising potential in the treatment of colitis.Methods: As a proof of concept, the efficacy of ELNs from edible Zanthoxylum bungeanum (ZbELNs) in protecting macrophages from inflammation was determined by in vitro experiments. Moreover, we assess the therapeutic effect of ZbELNs to colitis in a mouse model.Results: ZbELNs were found to have an ideal particle size (160.0 nm) and contain a large number of lipids, some functional proteins or metabolites, and many small RNA molecules. The in vitro experiment results revealed that ZbELN pretreatment increased cell vitality and decreased the levels of pro-inflammatory cytokines. Furthermore, the in vivo experiments indicated that oral administration of ZbELNs can significantly reduce disease activity index, increase colon length, and inhibit colon wall thickening, thereby alleviating acute colitis in dextran sulfate sodium-induced model mice. In addition, ZbELN treatment can reduce the degree of histological damage in the colon and suppress pro-inflammatory cytokines levels in mice serum. Notably, miRNA-1 and miRNA-21 in ZbELNs showed similar therapeutic effects on macrophage inflammation.Conclusion: These findings suggest that ZbELNs are a novel natural nanomedicine with promising therapeutic potential for the treatment of colonic diseases.Keywords: exosome-like nanoparticles, colitis, inflammation, Zanthoxylum bungeanum, disease activity index