Sweroside ameliorates intestinal mucosal microcirculatory disturbances in ulcerative colitis mice by modulating the VEGF and Hippo signaling pathways

Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease closely linked to intestinal mucosal microcirculatory dysfunction. Sweroside (SOS), a natural iridoid glycoside derived from plants such as Swertia mussotii , Swertia pseudochinensis , and Lonicera japonica , exhibits anti-inflammatory properties. Yet, its therapeutic potential and mechanisms in UC remain unexplored. This study aimed to investigate the effects of SOS on dextran sulfate sodium (DSS)-induced UC and its underlying mechanisms. Methods A DSS-induced UC mouse model was established to evaluate the efficacy of SOS. Inflammatory cytokine levels, intestinal barrier function (assessed via MUC2 immunofluorescence, FITC-dextran permeability, and tight junction protein analysis), and mucosal microcirculation (measured by Laser Speckle Contrast Imaging) were examined. Angiogenesis and endothelial cell (EC) damage were analyzed using ELISA, immunohistochemistry, and transmission electron microscopy. Transcriptomics and molecular docking were utilized to investigate SOS-mediated pathways, with subsequent validation by qRT-PCR, western blot, and immunofluorescence. Additionally, a cellular injury model was generated by treating human umbilical vein endothelial cells (HUVECs) with DSS. Cellular inflammatory and angiogenesis-related factors were quantified via ELISA, while migration and angiogenesis capabilities of HUVECs were assessed through scratch and tube-forming assays. The expression of the VEGF and Hippo pathway-related proteins was determined by western blot. Results SOS significantly ameliorated UC symptoms, reducing weight loss, diarrhea, and DAI scores while suppressing inflammatory infiltration and cytokine release. SOS enhanced intestinal barrier integrity via tight junction upregulation and improved microcirculation by attenuating EC injury and angiogenesis. Mechanistically, SOS regulated the VEGF and Hippo pathways, a key regulator of angiogenesis, as confirmed by transcriptomics and molecular docking. In vitro , SOS protected HUVECs from DSS-induced inflammation and angiogenesis, confirming the improvement of mucosal microcirculation by modulating VEGF and Hippo pathways. Conclusions SOS ameliorates DSS-induced UC by impacting the VEGF and Hippo pathways, thereby suppressing ECs' angiogenesis, restoring mucosal microcirculation, and mitigating intestinal inflammation. These findings highlight SOS as a promising therapeutic candidate for UC.