BACKGROUND
Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder characterized by compromised intestinal barrier integrity.
PURPOSE
This study aimed to elucidate the therapeutic mechanisms of Tetrastigma hemsleyanum polysaccharides (THP) in restoring the gut vascular barrier (GVB) via the sphingosine-1-phosphate (S1P)/S1P receptor 2 (S1PR2) signaling axis.
METHODS
A dextran sulfate sodium (DSS)-induced murine colitis model and tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-stimulated human umbilical vein endothelial cells (HUVECs) were used. Multiple techniques including laser speckle contrast imaging, transmission electron microscopy, immunofluorescence, Western blotting, Transwell permeability assays, tube formation assays, and gene silencing were employed to evaluate the effects of THP.
RESULTS
THP treatment significantly ameliorated clinical symptoms, histopathological damage, and pro-inflammatory cytokine secretion in colitis mice. Specifically, THP preserved GVB integrity by upregulating tight junction proteins (ZO-1, Claudin-1, Occludin) and adherens junction proteins (VE-cadherin, β-catenin) proteins, thereby reducing vascular permeability and suppressing pathological angiogenesis. Mechanistically, THP effectively modulated the S1P/S1PR2 signaling axis, there restoring endothelial homeostasis.
CONCLUSION
Collectively, this study demonstrates that THP alleviates IBD by repairing the GVB through the S1P/S1PR2 axis, providing a mechanistic basis for GVB-targeted therapeutic strategies.
Wenxuan Li, Yi-Wen Hu, Menghan Yang et al.· Phytomedicine· 0 citations
Ulcerative colitis (UC) is an immune-mediated chronic inflammatory bowel disease that severely impairs patients’ quality of life. Efficient oral colon-targeted delivery systems are urgently needed to improve local therapeutic efficacy while minimizing systemic exposure. Herein, we developed a pH-responsive Eudragit S100-coated coacervate microdroplet system for the oral delivery of natural Bletilla striata polysaccharide (BSP), termed BSP@EU-Coac. The optimized BSP@EU-Coac microdroplets exhibited a spherical morphology with an average hydrodynamic diameter of 3.86 ± 0.82 μm, an encapsulation efficiency of 85.03 ± 3.66%, and a drug loading capacity of 9.29 ± 0.93%. In vitro release studies showed that BSP@EU-Coac effectively limited premature BSP release under simulated gastric and small intestinal conditions, while achieving pH-triggered sustained release in simulated colonic medium, with a cumulative release of approximately 88.25% within 96 h. In vitro assays further demonstrated that BSP@EU-Coac showed good cytocompatibility at the working concentration and markedly reduced intracellular ROS levels, with ROS fluorescence intensity decreased by 53.95% and 51.13% in RAW264.7 macrophages and Caco-2 cells, respectively. After oral administration, fluorescence imaging confirmed that BSP@EU-Coac preferentially accumulated in the inflamed colon and maintained detectable colonic retention for up to 24 h. In a DSS-induced colitis mouse model, BSP@EU-Coac significantly alleviated UC symptoms, as evidenced by improved body weight recovery, reduced disease activity index, and restoration of colon length from 4.99 ± 1.23 cm in the model group to 8.66 ± 1.92 cm. Mechanistically, BSP@EU-Coac modulated macrophage polarization by reducing the M1-like CD86⁺CD206⁻ population from 29.26% to 8.95% and increasing the M2-like CD86⁻CD206⁺ population to 20.70%, accompanied by suppressed pro-inflammatory cytokine expression, enhanced tight junction protein expression, reduced oxidative stress, and partial restoration of gut microbiota homeostasis. Overall, this study demonstrates that BSP@EU-Coac is a promising oral colon-targeted polysaccharide delivery platform for UC therapy through integrated regulation of oxidative stress, immune response, epithelial barrier repair, and gut microbiota.
Qiantao Zhang, L. Chai, Hui Liu et al.· Journal of Nanobiotechnology· 0 citations
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