评估一种新型联吡唑衍生物在缓解实验性结肠炎症状方面的抗炎功效

Yousra Bseiso, Omar Gammoh, Mohammad Alqudah, Sara Altaber, Esam Qnais, Mohammed Wedyan, Abdelrahim Alqudah, Badriyah S Alotaibi
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引用次数: 0

摘要

目的:本研究旨在评估新型化合物 2', 3, 3, 5'-Tetramethyl-4'-nitro-2'H-1, 3'-bipyrazole (TMNB) 治疗结肠炎的疗效:背景:炎症性肠病(IBD)是一种慢性胃肠道炎症,目前有效的治疗方法有限。探索新的治疗药物对于推进治疗方案至关重要:评估 TMNB 在减轻小鼠实验性结肠炎症状方面的效果,并将其与标准治疗药物磺胺沙拉嗪的效果进行比较:方法:诱导小鼠患实验性结肠炎,然后用 50、100 和 150 毫克/千克剂量的 TMNB 治疗。结果根据结肠炎症状、结肠损伤、疾病活动指数(DAI)评分以及炎症标志物(包括一氧化氮和髓过氧化物酶水平)进行评估。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):结果:TMNB 治疗可明显缓解结肠炎症状(100 和 150 毫克/千克)。这些较高剂量明显减轻了结肠损伤、炎症、充血、水肿和溃疡(p<0.01)。治疗还有效降低了疾病活动指数(DAI)评分,明显改善了结肠炎的临床症状(100 毫克/千克,p<0.05;150 毫克/千克,p<0.01)。此外,TMNB 还大大降低了髓过氧化物酶 (MPO) 水平,表明中性粒细胞活性和炎症有所降低(100 毫克/千克,p<0.05;150 毫克/千克,p<0.01),并降低了一氧化氮 (NO) 水平,表明氧化应激有所减轻(100 毫克/千克,p<0.05;150 毫克/千克,p<0.01)。治疗还显著降低了脾脏细胞的增殖(100 毫克/千克,p<0.05; 150 毫克/千克,p<0.01)和促炎细胞因子水平,TNF-α、IL-1β和 IL-6 的降幅与磺胺沙拉嗪的降幅相当(p<0.01)。此外,TMNB 还能有效降低 IL-1β、IL-6、TNF-α、COX2 和 iNOS 的浓度(p<0.01),这肯定了它的广谱抗炎和免疫调节作用:结论:TMNB 具有强大的抗炎和免疫调节活性,这表明 TMNB 可以成为治疗炎症性肠病的一种新疗法。这项研究证明,有必要进一步开展临床试验,探索 TMNB 对人体的疗效和安全性。
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Evaluating the Anti-inflammatory Efficacy of a Novel Bipyrazole Derivative in Alleviating Symptoms of Experimental Colitis.

Aims: 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.

Background: 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.

Objective: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

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