School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China (L.L., S.D., Y.X., H.S., M.Z., X.L., S.W., W.J.); Macau Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China (L.L., H.L.); Department of Pharmacy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China (Y.Z.); School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China (G.Z.); and Shaanxi Engineering Research Center of Cardiovascular Drugs Screening and Analysis, Xi'an, China (S.D., Y.X., H.S., M.Z., X.L., S.W., W.J.).
School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, China (L.L., S.D., Y.X., H.S., M.Z., X.L., S.W., W.J.); Macau Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China (L.L., H.L.); Department of Pharmacy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China (Y.Z.); School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China (G.Z.); and Shaanxi Engineering Research Center of Cardiovascular Drugs Screening and Analysis, Xi'an, China (S.D., Y.X., H.S., M.Z., X.L., S.W., W.J.)
J Pharmacol Exp Ther. 2024 Jun 21;390(1):116-124. doi: 10.1124/jpet.123.002020.
Ulcerative colitis (UC) is an immune-mediated inflammatory disease that can lead to persistent damage and even cancer without any intervention. Conventional treatments can alleviate UC symptoms but are costly and cause various side effects. Tauroursodeoxycholic acid (TUDCA), a secondary bile acid derivative, possesses anti-inflammatory and cytoprotective properties for various diseases, but its potential therapeutic benefits in UC have not been fully explored. Mice were subjected to colitis induction using 3% dextran sulfate sodium (DSS). The therapeutic effect of TUDCA was evaluated by body weight loss, disease activity index (DAI), colon length, and spleen weight ratio. Tissue pathology was assessed using H&E staining, while the levels of pro-inflammatory and anti-inflammatory cytokines in colonic tissue were quantified via ELISA. Tight junction proteins were detected by immunoblotting and intestinal permeability was assessed using fluorescein isothiocyanate (FITC)-dextran. Moreover, the gut microbiota was profiled using high-throughput sequencing of the 16S rDNA gene. TUDCA alleviated the colitis in mice, involving reduced DAI, attenuated colon and spleen enlargement, ameliorated histopathological lesions, and normalized levels of pro-inflammatory and anti-inflammatory cytokines. Furthermore, TUDCA treatment inhibited the downregulation of intestinal barrier proteins, including zonula occludens-1 and occludin, thus reducing intestinal permeability. The analysis of gut microbiota suggested that TUDCA modulated the dysbiosis in mice with colitis, especially for the remarkable rise in TUDCA exerted a therapeutic efficacy in DSS-induced colitis by reducing intestinal inflammation, protecting intestinal barrier integrity, and restoring gut microbiota balance. SIGNIFICANCE STATEMENT: This study demonstrates the potential therapeutic benefits of Tauroursodeoxycholic acid (TUDCA) in ulcerative colitis. TUDCA effectively alleviated colitis symptoms in mice, including reducing inflammation, restoring intestinal barrier integrity and the dysbiosis of gut microbiota. This work highlights the promising role of TUDCA as a potentially alternative treatment, offering new insights into managing this debilitating condition.
溃疡性结肠炎（UC）是一种免疫介导的炎症性疾病，如果不进行任何干预，它可能会导致持续的损伤，甚至癌症。传统的治疗方法可以缓解 UC 的症状，但成本高昂且会引起各种副作用。牛磺熊脱氧胆酸（TUDCA）是一种次级胆酸衍生物，具有抗炎和对多种疾病的细胞保护作用，但它在 UC 中的潜在治疗益处尚未得到充分探索。使用 3%葡聚糖硫酸钠（DSS）诱导小鼠结肠炎。通过体重减轻、疾病活动指数（DAI）、结肠长度和脾脏重量比评估 TUDCA 的治疗效果。使用 H&E 染色评估组织病理学，通过 ELISA 定量测定结肠组织中促炎和抗炎细胞因子的水平。通过免疫印迹检测紧密连接蛋白，通过荧光素异硫氰酸酯（FITC）-葡聚糖评估肠道通透性。此外，使用 16S rDNA 基因高通量测序对肠道微生物群进行分析。TUDCA 减轻了小鼠的结肠炎，包括降低 DAI、减轻结肠和脾脏肿大、改善组织病理学损伤以及使促炎和抗炎细胞因子的水平正常化。此外，TUDCA 治疗抑制了肠道屏障蛋白（包括闭锁蛋白-1 和紧密连接蛋白）的下调，从而降低了肠道通透性。肠道微生物群分析表明，TUDCA 调节了结肠炎小鼠的失调，特别是对 TUDCA 引起的结肠炎具有治疗作用，可通过减轻肠道炎症、保护肠道屏障完整性和恢复肠道微生物群平衡来发挥治疗作用。意义声明：本研究表明牛磺熊脱氧胆酸（TUDCA）在溃疡性结肠炎中的潜在治疗益处。TUDCA 有效缓解了小鼠的结肠炎症状，包括减轻炎症、恢复肠道屏障完整性和肠道微生物群失调。这项工作强调了 TUDCA 作为一种潜在替代治疗方法的有前途的作用，为治疗这种使人衰弱的疾病提供了新的见解。
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