Integrating 16srRNA sequencing, non-targeted metabolomics, and transcriptome sequencing to explore the mechanism of Total glucosides of paeony alleviating ulcerative colitis

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography B Pub Date : 2025-04-19 DOI:10.1016/j.jchromb.2025.124600

Jianglin Chen , Qi Yuan , Cui Yu , Jie Fu , Penghao Wang , Shuiyan Tang , Xiaochen Lin , Qiyang Shou , Huiying Fu

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引用次数: 0

Abstract

Total glucosides of paeony (TGP), an active ingredient extracted from the dried root of Paeonia lactiflora Pall., has been approved in China for the treatment of various autoimmune diseases. However, the role and mechanism of TGP in UC have yet to be fully elucidated. This study aims to investigate the regulatory effects and underlying mechanisms of TGP on intestinal homeostasis disruption and immune imbalance in a mouse model of dextran sulfate sodium (DSS)-induced colitis. The results showed that TGP alleviated DSS induced body weight loss, colonic shortening and histopathological changes in mice, and also enhanced the integrity of the intestinal barrier by up-regulating the expression of ZO-1, Occludin and tight junction protein in the colon. The results of 16S and antibiotic cocktail (ABX) experiments showed that TGP alleviated colitis by inhibiting Th17 cell differentiation by correcting intestinal microbial imbalance in UC mice. Mechanism studies showed that TGP inhibited the activation of JAK2/STAT3 signaling pathway in UC mice, and decreased the levels of inflammatory factors in colon supernatant and serum. Importantly, TGP regulates JAK2/STAT3 to inhibit Th17 cell differentiation depending on gut flora. In addition, TGP can also improve the metabolic imbalance in UC mice, especially purine metabolism. In conclusion, TGP promotes the normalization of purine metabolism and relies on gut microbiota to regulate JAK2/STAT3 pathway, inhibit Th17 cell differentiation, and alleviate colitis. Our findings highlight TGP as a promising treatment candidate for ulcerative colitis.

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整合16srRNA测序、非靶向代谢组学和转录组测序，探讨芍药总苷缓解溃疡性结肠炎的机制

芍药总苷（TGP），从芍药干根中提取的活性成分。在中国已被批准用于治疗多种自身免疫性疾病。然而，TGP在UC中的作用和机制尚未完全阐明。本研究旨在探讨TGP对右旋糖酐硫酸钠（DSS）诱导的小鼠结肠炎模型中肠道稳态破坏和免疫失衡的调节作用及其机制。结果表明，TGP可减轻DSS诱导小鼠的体重减轻、结肠缩短和组织病理学改变，并通过上调结肠ZO-1、Occludin和紧密连接蛋白的表达，增强肠道屏障的完整性。16S和抗生素鸡尾酒（ABX）实验结果表明，TGP通过纠正UC小鼠肠道微生物失衡，抑制Th17细胞分化，从而减轻结肠炎。机制研究表明，TGP抑制UC小鼠JAK2/STAT3信号通路的激活，降低结肠上清和血清中炎症因子的水平。重要的是，TGP调节JAK2/STAT3抑制Th17细胞分化依赖于肠道菌群。此外，TGP还能改善UC小鼠的代谢失衡，尤其是嘌呤代谢。综上所述，TGP促进嘌呤代谢正常化，并依赖肠道菌群调节JAK2/STAT3通路，抑制Th17细胞分化，缓解结肠炎。我们的研究结果强调TGP是溃疡性结肠炎的一种有希望的治疗候选药物。

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来源期刊

Journal of Chromatography B 医学-分析化学

CiteScore

5.60

自引率

3.30%

发文量

306

审稿时长

44 days

期刊介绍： The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.