Miljković Radmila, Marinković Emilija, Prodić Ivana, Kovačević Ana, Protić-Rosić Isidora, Vasić Marko, Lukić Ivana, Gavrović-Jankulović Marija, Stojanović Marijana
Department of Research and Development, Institute of Virology, Vaccines and Sera "Torlak", 11221 Belgrade, Serbia.
Institute for Immunology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
Biomolecules. 2025 Mar 25;15(4):476. doi: 10.3390/biom15040476.
: The global burden of inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, is constantly rising. As IBDs significantly reduce patients' quality of life, prevention and efficient treatment of IBDs are of paramount importance. Although the molecular mechanisms underlying IBD pathogenesis are still not completely understood, numerous studies indicate the essential role of oxidative stress in the progression of the diseases. : The aim of this study was to investigate whether prophylactic administration of recombinant banana lectin (rBanLec) could positively affect antioxidative mechanisms in the colon and thus prevent or alleviate the severity of experimental colitis induced in C57BL/6 mice. : The prophylactic potential of rBanLec, a mannose-binding lectin with immunomodulatory properties, was investigated in a model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in C57BL/6 mice. Mice received rBanLec at various doses (0.1, 1 and 10 μg/mL) before the induction of colitis. The severity of the disease was assessed by weight loss and reduction in colon length, and correlated with histopathological findings, cytokine milieu, and oxidative stress markers in the colon. : The obtained results revealed that pretreatment with a low dose of rBanLec (0.1 μg/mL) significantly reduced the severity of TNBS-induced colitis, as indicated by reduced weight loss, less severe histopathological damage, and a favorable anti-inflammatory cytokine milieu (increased IL-10 and TGFβ). In addition, rBanLec pretreatment improved the activity of antioxidant enzymes (SOD, CAT, and GST) and reduced markers of oxidative stress such as nitric oxide levels at the peak of the disease. In contrast, higher doses of rBanLec exacerbated inflammatory responses. : Our findings indicate that at low doses rBanLec can alleviate the severity of colitis by modulating oxidative stress and promoting anti-inflammatory cytokine responses, positioning rBanLec as a potential candidate for treating IBDs.
包括溃疡性结肠炎和克罗恩病在内的炎症性肠病（IBD）的全球负担正在持续上升。由于IBD显著降低患者的生活质量，因此IBD的预防和有效治疗至关重要。尽管IBD发病机制的分子机制仍未完全阐明，但大量研究表明氧化应激在疾病进展中起着关键作用。本研究的目的是调查预防性给予重组香蕉凝集素（rBanLec）是否能对结肠中的抗氧化机制产生积极影响，从而预防或减轻C57BL/6小鼠实验性结肠炎的严重程度。在C57BL/6小鼠2,4,6-三硝基苯磺酸（TNBS）诱导的结肠炎模型中研究了具有免疫调节特性的甘露糖结合凝集素rBanLec的预防潜力。在诱导结肠炎之前，小鼠接受不同剂量（0.1、1和10μg/mL）的rBanLec。通过体重减轻和结肠长度缩短评估疾病严重程度，并与组织病理学结果、细胞因子环境和结肠中的氧化应激标志物相关联。获得的结果表明，低剂量rBanLec（0.1μg/mL）预处理显著降低了TNBS诱导的结肠炎的严重程度，表现为体重减轻减少、组织病理学损伤较轻以及有利的抗炎细胞因子环境（IL-10和TGFβ增加）。此外，rBanLec预处理提高了抗氧化酶（SOD、CAT和GST）的活性，并降低了疾病高峰期氧化应激标志物如一氧化氮水平。相比之下，较高剂量的rBanLec加剧了炎症反应。我们的研究结果表明，低剂量的rBanLec可以通过调节氧化应激和促进抗炎细胞因子反应来减轻结肠炎的严重程度，使rBanLec成为治疗IBD的潜在候选药物。
