Ulcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.

中文翻译：

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Desmethylbellidifolin 减轻葡聚糖硫酸钠诱导的结肠炎：对肠道屏障、肠道炎症和肠道微生物群的影响

溃疡性结肠炎已被认为是一种主要影响结肠和直肠的慢性炎症性疾病。临床上，氨基水杨酸盐​​、类固醇、免疫抑制剂和生物药物一般用于治疗疾病进展不同阶段的溃疡性结肠炎。然而，由于经常出现耐药性，这些药物的治疗效果并不能令患者满意。在此，我们报道了去甲基贝里多林（一种从急性龙胆草中分离出来的呫吨酮）在葡聚糖硫酸钠诱导的小鼠结肠炎中的抗溃疡性结肠炎活性。C57BL/6 小鼠在饮用水中用 2% 葡聚糖硫酸钠处理以诱导急性结肠炎。Desmethylbellidifolin 或巴柳氮钠每天口服一次。收集生物样本进行免疫组织学分析，肠道屏障功能评估、细胞因子测量和肠道微生物群分析。结果表明，去甲基贝利叶林可减轻硫酸葡聚糖钠诱导的小鼠的结肠缩短和体重减轻。在治疗 9 天后，去甲基贝利叶林也降低了疾病活动指数。此外，desmethylbellidifolin 通过抑制 IL-6 和肿瘤坏死因子-α 的表达显着改善结肠炎症。通过增加 occludin、ZO-1 和 claudins 的水平，去甲基贝利叶林增强了肠上皮屏障。此外，desmethylbellidifolin 调节了由硫酸葡聚糖钠引起的肠道菌群失调。这些发现表明，去甲基甜菜碱至少部分有效地改善了实验性溃疡性结肠炎，