摘要Ulcerative colitis(UC)is a chronic inflammatory disorder with a complex etiology,character-ized by intestinal inflammation and barrier dysfunction.Platycodon grandiflorus polysacchar-ides(PGP),the primary component of Platycodon grandiflorus,and hesperidin(Hesp),a prominent active component in Citrus aurantium L.(CAL),have both demonstrated anti-in-flammatory properties.This study aims to elucidate the underlying mechanism of the syner-gistic effect of PGP combined with Hesp on UC,focusing on the coordinated interaction between the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)and Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathways.A mouse model of UC induced by dextran sulfate sodium(DSS)and a cell model using lipopoly-saccharide(LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechan-ism of action.The results indicated that compared to the effects of either drug alone,the com-bination of PGP and Hesp significantly modulated inflammatory factor levels,inhibited oxidat-ive stress,regulated colonic mucosal immunity,suppressed apoptosis,and restored intestin-al barrier function in vitro and in vivo.Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway,while Hesp significantly inhibited the JAK2/STAT3 signaling pathway.The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways.These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis,potentially mediated through the phosphatase and tensin homolog(PTEN)/PI3K/AKT and interleukin-6(IL-6)/JAK2/STAT3 signaling pathways.