Vesicle-like nanoparticles extracted from Pueraria lobata decoction alleviate colitis by modulating the intestinal microbiota

Aim: This study aimed to investigate whether vesicle-like nanoparticles derived from the GeGen decoction (GGD-PDVLNs) represent a key bioactive component responsible for its anti-colitis effects and to elucidate their underlying mechanisms, particularly focusing on gut microbiota modulation. Methods: The GeGen decoction (GGD) was subjected to differential centrifugation following boiling, yielding vesicle-like nanoparticles. Structural analysis confirmed that these nanoparticles have a lipid bilayer and can resist digestion by simulated gastrointestinal fluids. These nanoparticles were administered orally to mice with chronic colitis induced by dextran sulfate sodium to evaluate their therapeutic effects. Results: GGD-PDVLNs effectively mitigated intestinal inflammation by reducing the secretion of pro-inflammatory cytokines [interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha (TNF-α)], elevating levels of the anti-inflammatory cytokine IL-10, alleviating intestinal damage, and enhancing intestinal barrier function, all while exhibiting a favorable biosafety profile. Notably, their therapeutic action depended on gut microbiota modulation. GGD-PDVLNs restored microbial homeostasis, increased microbial diversity, and enriched probiotic populations. In pseudo-germ-free mice, GGD-PDVLNs lost efficacy, confirming microbiota-dependent mechanisms. Conclusion: Vesicle-like nanoparticles are an important active component of GGD. Our findings demonstrate that GGD-PDVLNs significantly ameliorate colonic inflammation through microbiota-dependent mechanisms.