Anti-inflammatory activity and mechanism of Lonicera japonica Thunb.-derived extracellular vesicle-like particles

Chen Yuanjun; Lin Sixing; Ji Lichun; Li Dongxiao; Liao Guangzhi; Lin Xingdong

doi:10.12307/2026.153

Abstract：BACKGROUND:Recently,nanotechnology has shown potential in anti-inflammatory treatment,but nanodrug systems face challenges in production costs,process complexity,and biosafety.Chinese herbal medicine-derived vesicle technology,with advantages like abundant sources and good biocompatibility,has emerged as a new research hotspot in traditional Chinese medicine. OBJECTIVE:To explore the anti-inflammatory biological activity and mechanism of Lonicera japonica Thunb.-derived extracellular vesicle-like particles. METHODS:Lonicera japonica Thunb.-derived extracellular vesicle-like particles were extracted using ultracentrifugation and characterized.The uptake of Lonicera japonica Thunb.-derived extracellular vesicle-like particles by RAW264.7 cells and their biocompatibility were evaluated using CCK-8 assays,flow cytometry,and confocal microscopy.A lipopolysaccharide-induced RAW264.7 cell inflammation model was established to investigate the effects of Lonicera japonica Thunb.-derived extracellular vesicle-like particles on inflammatory mediators and macrophage phenotypes.Transcriptomics was used to elucidate the anti-inflammatory mechanisms of Lonicera japonica Thunb.-derived extracellular vesicle-like particles. RESULTS AND CONCLUSION:(1)Lonicera japonica Thunb.-derived extracellular vesicle-like particles had a particle size of(79.42±23.12)nm,with typical cup-shaped vesicle and membrane structures,and showed good stability in simulated gastrointestinal digestion.(2)Lonicera japonica Thunb.-derived extracellular vesicle-like particles were non-toxic to RAW264.7 cells,with an uptake rate exceeding 90%after 8 hours.(3)In inflammatory models,Lonicera japonica Thunb.-derived extracellular vesicle-like particles significantly reduced interleukin-6,interleukin-1β and cyclooxygenase-2 levels,inhibited M1 macrophage polarization,and restored interleukin-10 and CD206 levels.(4)Transcriptomic analysis suggests that Lonicera japonica Thunb.-derived extracellular vesicle-like particles exert anti-inflammatory effects by modulating key inflammatory signaling pathways such as tumor necrosis factor,nuclear factor κB,and Toll-like receptors.These findings demonstrate significant anti-inflammatory activity of Lonicera japonica Thunb.-derived extracellular vesicle-like particles,providing experimental evidence for their potential as a novel anti-inflammatory drug delivery system and offering a new option for treating inflammatory diseases.