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白头翁汤通过调控 FXR 和 TGR5 相关通路改善 DSS 诱导的溃疡性结肠炎,其作用机制与肠道微生物群和胆汁酸有关。

Baitouweng Tang ameliorates DSS-induced ulcerative colitis through the regulation of the gut microbiota and bile acids via pathways involving FXR and TGR5.

机构信息

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province, 730070, People's Republic of China.

出版信息

Biomed Pharmacother. 2021 May;137:111320. doi: 10.1016/j.biopha.2021.111320. Epub 2021 Feb 9.

DOI:10.1016/j.biopha.2021.111320
PMID:33578232
Abstract

In China, Baitouweng Tang (BTWT) is a commonly prescribed remedy for the treatment of ulcerative colitis (UC). Herein, the present study aims to assess the anti-colitis activity of BTWT and its underlying mechanisms in UC BALB/c mice. Induction of UC in BALB/c mice was carried out by adding 3.5% DSS in the drinking water of underlined mice. After UC induction, the mice were administrated with BTWT for 7 days. Clinical symptoms were assessed, followed by analyzing the bile acids (BAs) in serum, liver, colon, bile, and feces of UC mice through UPLC-MS/MS. The modified 16S rDNA high-throughput sequencing was carried out to examine the gut microbiota of feces. BTWT significantly improved the clinical symptoms such as and histological injury and colon shortening in UC induced mice. Furthermore, BTWT remarkably ameliorated colonic inflammatory response. After BTWT treatment, the increased concentrations of UDCA, HDCA, αMCA, βMCA, CA, and GLCA in UC were decreased, and the levels of some BAs, especially CA, αMCA, and βMCA were normalized. Moreover, the relative species abundance and gut microbiota diversity in the BTWT-exposed groups were found to be considerably elevated than those in the DSS-treated group. BTWT increased the relative abundance of Firmicutes, Proteobacteria, Actinobacteria, Tenericutes, and TM7, which were statistically lower in the fecal microbiota of UC mice. The relative abundance of Bacteroidetes was found to be elevated in the DSS group and normalized after BTWT treatment. BTWT increased the expression of FXR and TGR5 in the liver. BTWT administration improved DSS-induced mice signs by increasing the TGR5 and FXR expression levels. This result was achieved by the regulation of the BAs and gut microbiota.

摘要

在中国,白头翁汤(BTWT)是一种常用于治疗溃疡性结肠炎(UC)的方剂。本研究旨在评估 BTWT 对 UC BALB/c 小鼠的抗结肠炎活性及其作用机制。通过在饮水(3.5%DSS)中添加 DSS 诱导 BALB/c 小鼠 UC 模型。在诱导 UC 后,用 BTWT 对小鼠进行 7 天治疗。通过 UPLC-MS/MS 分析血清、肝脏、结肠、胆汁和粪便中的胆汁酸(BAs),评估 UC 小鼠的临床症状。采用改良 16S rDNA 高通量测序检测粪便微生物群。BTWT 显著改善了 UC 诱导小鼠的临床症状、组织学损伤和结肠缩短。此外,BTWT 显著改善了结肠炎症反应。BTWT 治疗后,UC 中 UDCA、HDCA、αMCA、βMCA、CA 和 GLCA 浓度增加得到改善,一些 BAs(特别是 CA、αMCA 和 βMCA)水平恢复正常。此外,BTWT 处理组的相对物种丰度和肠道微生物多样性明显高于 DSS 处理组。BTWT 增加了厚壁菌门、变形菌门、放线菌门、柔膜菌门和 TM7 的相对丰度,这些在 UC 小鼠粪便微生物群中的丰度较低。拟杆菌门的相对丰度在 DSS 组中升高,BTWT 治疗后恢复正常。BTWT 增加了肝脏中 FXR 和 TGR5 的表达。BTWT 通过调节 BAs 和肠道微生物群来改善 DSS 诱导的小鼠症状,增加 TGR5 和 FXR 表达水平。

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