Taxus chinensis-Derived Nanovesicles Alleviate Mouse Colitis by Inhibiting Inflammatory Cytokines and Restoring Gut Microbiota

Qianyuan Gong,1,* Junqing Hu,2,3,* Chunlan Pu,1 Zihao Zhao,1 Yuanbiao Guo1 1Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, 610031, People’s Republic of China; 2Obesity and Metabolism Medicine-Engineering Integration Laboratory, Department of General Surgery, The Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, 610031, People’s Republic of China; 3The Center for Obesity and Metabolic Health, Department of General Surgery, The Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, 610031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qianyuan Gong, Email [email protected]: Recent research has increasingly focused on plant-derived products as potential alternatives to chemotherapeutic agents, aiming to reduce side effects. Among these, plant-derived nanovesicles (NVs) have garnered significant attention for their potential in treating colitis.Methods: In this study, we extracted NVs from the leaves (LNVs) and stems (SNVs) of Taxus, a well-known natural anti-cancer plant. The targeting ability of these NVs was evaluated in the mouse colon using an IVIS imaging system. Additionally, we assessed the therapeutic effects of these plant-derived NVs on ulcerative colitis in a mouse model.Results: Our findings reveal that the NVs exhibit an ideal vesicle size of 150.0 nm and contain a rich array of lipids, functional proteins, and bioactive small molecules. In vitro anti-inflammatory experiments demonstrated that both LNVs and SNVs enhanced cell viability and reduced levels of pro-inflammatory cytokines. Importantly, neither LNVs nor SNVs induced significant cytotoxicity. In vivo, oral administration of LNVs and SNVs ameliorated colitis-related symptoms in mice and accelerated colitis resolution by suppressing the TLR4/MyD88/NF-κB pathway and reducing levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Furthermore, 16S rDNA sequencing data suggested that LNVs play a crucial role in regulating gut microbiota.Conclusion: Collectively, our findings suggest that plant-derived NVs from Taxus represent a promising novel natural nanomedicine for use as an anti-inflammatory agent in the treatment of colonic diseases.Keywords: colitis, plant-derived nanovesicles, gut microbiota