"One stone three birds": Andrographis paniculata -derived exosome-like nanoparticles mitigate dextran sulfate sodium-induced colitis.

BACKGROUND: Ulcerative colitis (UC), a chronic inflammatory bowel disease, is characterized by a multifactorial etiology and limited therapeutic options. Recent advancements in plant-derived exosome-like nanoparticles (PDENs) have demonstrated promising potential for UC treatment. This study explored the therapeutic efficacy of Andrographis paniculata -derived exosome-like nanoparticles (APELNs) in alleviating dextran sodium sulfate (DSS)-induced colitis. METHODS: APELNs were isolated and purified using sucrose gradient centrifugation and subsequently characterized through visualization techniques. Their stability was assessed under simulated stomach-like and intestine-like conditions. The therapeutic potential of APELNs was evaluated through both in vivo and in vitro experiments. In addition, the biosafety of APELNs was comprehensively analyzed in these settings. RESULTS: APELNs exhibited excellent stability and biosafety, with a targeted accumulation in inflamed colonic tissues under gastrointestinal conditions. The nanoparticles displayed a desirable size (about 180 nm) and a negative zeta potential (-40 mV). Treatment with APELNs significantly ameliorated colonic pathologies in vivo and suppressed the expression of pro-inflammatory cytokines in vitro . Mechanistically, APELNs enhanced gut microbiota richness and diversity, fostering the growth of the probiotic Lactobacillus murinus . Moreover, APELNs reduced intestinal permeability and preserved intestinal barrier integrity by upregulating tight junction proteins, including Claudin-1, zonula occludens-1, Mucin2, and anti-occludin. Importantly, oral administration of APELNs shifted macrophage polarization in the colon, inhibiting the pro-inflammatory M1 subset while promoting the anti-inflammatory M2 subset. This polarization was mediated through the activation of the phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) and Janus tyrosine kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways and the upregulation of interleukin-4 receptor expression. CONCLUSION: These findings highlighted the potential of APELNs as a novel therapeutic strategy for UC, offering a promising alternative for effective disease management.