关键词: DSS-induced Colitis NLRP3 inflammasome PPARγ scopoletin ulcerative colitis

来  源:   DOI:10.1007/s10753-024-02048-9

Abstract:
This study aimed to investigate the therapeutic potential of scopoletin in ulcerative colitis, with a primary focus on its impact on crucial inflammatory pathways and immune responses. A male mouse model of DSS-induced colitis was employed with six distinct groups: a control group, a group subjected to DSS only, three groups treated with varying scopoletin doses, and the final group treated with dexamethasone. The investigation included an assessment of the effects of scopoletin on colitis symptoms, including alterations in body weight, Disease Activity Index (DAI), and histopathological changes in colonic tissue. Furthermore, this study scrutinized the influence of scopoletin on cytokine production, PPARγ and NF-κB expression, NLRP3 inflammasome, and the composition of intestinal bacteria. Scopoletin treatment yielded noteworthy improvements in DSS-induced colitis in mice, as evidenced by reduced weight loss and colonic shortening (p < 0.05, < 0.01, respectively). It effectively diminished TNF-α, IL-1β, and IL-12 cytokine levels (p < 0.01, p < 0.05), attenuated NLRP3 inflammasome activation and the associated cytokine release (p < 0.05, p < 0.01), and modulated the immune response by elevating PPARγ expression while suppressing NF-κB pathway activation (p < 0.05, p < 0.01). Additionally, scopoletin induced alterations in the gut microbiota composition, augmenting beneficial Lactobacillus and Bifidobacteria while reducing E. coli (p < 0.05). It also enhanced tight junction proteins, signifying an improvement in the intestinal barrier integrity (p < 0.05, < 0.01). Scopoletin is a promising therapeutic agent for managing ulcerative colitis, showing benefits that extend beyond mere anti-inflammatory actions to encompass regulatory effects on gut microbiota and restoration of intestinal integrity.
摘要:
本研究旨在探讨在溃疡性结肠炎中的治疗潜力。主要关注其对关键炎症途径和免疫反应的影响。使用DSS诱导的结肠炎的雄性小鼠模型,有六个不同的组:对照组,仅接受DSS的组,三组用不同剂量的星保灵治疗,最后一组用地塞米松治疗。该调查包括评估了司可利坦对结肠炎症状的影响,包括体重的改变,疾病活动指数(DAI),结肠组织病理改变.此外,这项研究仔细研究了三氯乙素对细胞因子产生的影响,PPARγ和NF-κB表达,NLRP3炎性体,和肠道细菌的组成。在DSS诱导的小鼠结肠炎中,Scopoetin治疗产生了显著的改善,如体重减轻和结肠缩短所证明的(分别为p<0.05,<0.01)。它有效地减少了TNF-α,IL-1β,和IL-12细胞因子水平(p<0.01,p<0.05),减弱NLRP3炎性体激活和相关的细胞因子释放(p<0.05,p<0.01),并通过提高PPARγ表达同时抑制NF-κB通路激活来调节免疫应答(p<0.05,p<0.01)。此外,sepodetin诱导肠道微生物群组成的改变,增加有益的乳杆菌和双歧杆菌,同时减少大肠杆菌(p<0.05)。它还增强了紧密连接蛋白,表明肠屏障完整性的改善(p<0.05,<0.01)。Scopoletin是一种有前途的治疗溃疡性结肠炎的药物,显示出超越单纯抗炎作用的益处,包括对肠道微生物群的调节作用和肠道完整性的恢复。
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