Kuijie decoction ameliorates ulcerative colitis by affecting intestinal barrier functions, gut microbiota, metabolic pathways and Treg/Th17 balance in mice
Kuijie decoction ameliorates ulcerative colitis by affecting intestinal barrier functions, gut microbiota, metabolic pathways and Treg/Th17 balance in mice
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DOI：
10.1016/j.jep.2023.117316
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发表时间：
2023-10-23
影响因子：
5.4
通讯作者：
Yu，Qin
中科院分区：
文献类型：
--
作者：
Peng，Kaixin;Xia，Suhong;Yu，Qin
民族药理学相关性目前，溃疡性结肠炎（UC）的临床治疗方法有限，难以取得满意的疗效。中医药在UC治疗中的作用非常复杂。溃结汤作为经典中医药，在临床上广泛应用于治疗UC，但其作用机制尚不清楚，本研究旨在探讨溃结汤对UC的保护作用及其机制。以体重、结肠长度和结肠组织病理学等临床症状来衡量结肠炎的严重程度。定量炎性细胞因子和紧密连接蛋白的表达。采用16 S rRNA和非靶向代谢组学方法，分别观察中药复方对肠道植物群和肠道代谢的影响。流式细胞仪检测脾脏中Th 17细胞和TcB细胞的比例。结果KJD治疗组小鼠的临床症状和组织学损伤明显减轻，如体重增加，疾病活动指数（DAI）评分降低，结肠长度延长。KJD的施用还导致炎性介质的下调，ZO-1、闭合蛋白的表达的上调和封闭蛋白-2的减少，以及针对DSS挑战的改变的微生物群组成（特别是毛螺菌科的增加）。KJD通过调节肠上皮屏障功能、肠道植物群和恢复Th 17/Treg平衡，维持肠道内稳态。KJD有可能成为UC的中医治疗方法。
Ethnopharmacological relevanceCurrently, the clinical treatment is limited and difficult to achieve satisfactory results for ulcerative colitis (UC). The role of traditional Chinese medicine (TCM) in the treatment of UC is very complex. Kuijie decoction (KJD) as a classic TCM, is widely used in the clinical treatment of UC, but the mechanism of its action is still unclear.Aim of the studyThis study is to investigate the protective effects of KJD on UC and the underlying mechanisms.Materials and methodsThe experimental model of UC was induced by DSS, and KJD was introduced into the model at the same time. Clinical symptoms, including the body weight, colon length and colon histopathological, were used to measure the severity of colitis. The expression of inflammatory cytokines and tight junction proteins was quantified. The effect of KJD on intestinal flora and intestinal metabolism was determined by 16S rRNA and untargeted metabolomics analysis, respectively. The proportion of Th17 cells and Tregs in the spleen was examined by flow cytometry.ResultsMice treated with KJD showed significantly alleviated clinical symptoms and histological damage, such as more body weight gain, lower disease activity index (DAI) score, and longer colon length. The administration of KJD also led to the down-regulation of inflammatory mediators, upregulation of the expression of ZO-1, occludin and decreased claudin-2, as well as altered microbiota composition against DSS challenges (especially an increase of Lachnospiraceae). KJD enhanced the percentage of Treg cells but decreased the proportion of Th17 cells to maintain intestinal homeostasis by improving gut microbiota metabolism.ConclusionsIn summary, KJD maintained intestinal epithelial homeostasis by regulating epithelial barrier function, intestinal flora, and restoring Th17/Treg balance. KJD has the potential to be a Chinese medicine treatment for UC.