Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa 13133, Jordan.
Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid 21163, Jordan.
Curr Mol Pharmacol. 2024;17(1):e18761429333261. doi: 10.2174/0118761429333261241021034043.
This aims to assess the efficacy of 2', 3, 3, 5'-Tetramethyl-4'-nitro-2'H-1, 3'-bipyrazole (TMNB), a novel compound, in colitis treatment.
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with limited effective treatments available. The exploration of new therapeutic agents is critical for advancing treatment options.
To assess the effect of TMNB in alleviating symptoms of experimental colitis in mice and to compare its effectiveness with that of sulfasalazine, a standard treatment.
Experimental colitis was induced in mice, which were subsequently treated with TMNB at dosages of 50, 100, and 150 mg/kg. The outcomes were evaluated based on colitis symptoms, Colon damage, Disease Activity Index (DAI) scores, and inflammation markers, including nitric oxide (NO) and myeloperoxidase (MPO) levels. Additional assessments included spleen cell proliferation, pro-inflammatory cytokine production (TNF-α, IL-6, IL-1β), and inflammatory genes expression (IL-1β, IL-6, TNF-α, COX2, and iNOS).
TMNB treatment significantly alleviated colitis symptoms (100 and 150 mg/kg). These higher doses notably reduced colonic damage, inflammation, hyperemia, edema, and ulceration (p<0.01). The treatment also effectively decreased Disease Activity Index (DAI) scores, demonstrating a marked improvement in clinical signs of colitis (100 mg/kg, p<0.05; 150 mg/kg, p<0.01). Additionally, TMNB substantially lowered myeloperoxidase (MPO) levels, indicating reduced neutrophil activity and inflammation (100 mg/kg, p<0.05; 150 mg/kg, p<0.01), and nitric oxide (NO) levels, suggesting diminished oxidative stress (100 mg/kg, p<0.05; 150 mg/kg, p<0.01). The treatment also led to a significant reduction in spleen cell proliferation (100 mg/kg, p<0.05; 150 mg/kg, p<0.01) and pro-inflammatory cytokine levels, with TNF-α, IL-1β, and IL-6 all showing decreases comparable to those observed with sulfasalazine (p<0.01). Moreover, TMNB effectively downregulated IL-1β, IL-6, TNF-α, COX2, and iNOS (p<0.01), affirming its broad-spectrum anti-inflammatory and immunomodulatory effects.
TMNB exhibits potent anti-inflammatory and immunomodulatory activities, suggesting that TMNB could be a new therapeutic agent for managing inflammatory bowel disease. This study supports the need for further clinical trials to explore TMNB's efficacy and safety in human subjects.
本研究旨在评估新型化合物 2', 3, 3, 5'-四甲基-4'-硝基-2'H-1, 3'-联吡唑（TMNB）在结肠炎治疗中的疗效。
炎症性肠病（IBD）是一种慢性胃肠道炎症性疾病，目前可用的有效治疗方法有限。探索新的治疗药物对于推进治疗选择至关重要。
评估 TMNB 缓解实验性结肠炎小鼠症状的效果，并将其与标准治疗药物柳氮磺胺吡啶进行比较。
在小鼠中诱导实验性结肠炎，随后用 50、100 和 150mg/kg 的 TMNB 进行治疗。根据结肠炎症状、结肠损伤、疾病活动指数（DAI）评分以及炎症标志物，包括一氧化氮（NO）和髓过氧化物酶（MPO）水平来评估结果。其他评估包括脾细胞增殖、促炎细胞因子产生（TNF-α、IL-6、IL-1β）和炎症基因表达（IL-1β、IL-6、TNF-α、COX2 和 iNOS）。
TMNB 治疗显著缓解了结肠炎症状（100 和 150mg/kg）。这些较高剂量显著减轻了结肠损伤、炎症、充血、水肿和溃疡（p<0.01）。治疗还有效地降低了疾病活动指数（DAI）评分，显示出结肠炎临床症状的明显改善（100mg/kg，p<0.05；150mg/kg，p<0.01）。此外，TMNB 显著降低了髓过氧化物酶（MPO）水平，表明中性粒细胞活性和炎症减少（100mg/kg，p<0.05；150mg/kg，p<0.01），同时降低了一氧化氮（NO）水平，表明氧化应激减轻（100mg/kg，p<0.05；150mg/kg，p<0.01）。治疗还导致脾细胞增殖显著减少（100mg/kg，p<0.05；150mg/kg，p<0.01）和促炎细胞因子水平降低，TNF-α、IL-1β和 IL-6 的降低与柳氮磺胺吡啶相当（p<0.01）。此外，TMNB 有效地下调了 IL-1β、IL-6、TNF-α、COX2 和 iNOS（p<0.01），证实了其广谱抗炎和免疫调节作用。
TMNB 表现出强大的抗炎和免疫调节活性，表明 TMNB 可能成为治疗炎症性肠病的新治疗药物。本研究支持进一步开展临床试验，以探索 TMNB 在人类受试者中的疗效和安全性。
