甘草调节肠道关节轴，缓解胶原蛋白诱发的类风湿性关节炎。

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2024-10-29 DOI:10.1016/j.phymed.2024.156203

Di Yang, Guangfu Lv, Yongxi Wu, Wentao Guo, Yuchen Wang, Jiannan Hu, Nian Li, Fei Zheng, Yulin Dai, Zifeng Pi, Hao Yue

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引用次数: 0

摘要

背景：类风湿性关节炎（RA类风湿性关节炎（RA）部分受到肠道屏障完整性的影响。甘草（GC）是一种药食同源的草药，具有很强的抗炎活性；然而，有关其在 RA 中作用机制的研究还很有限：本研究利用牛II型胶原蛋白诱导的关节炎大鼠模型，探讨了甘草如何影响肠道-关节轴以减少RA。研究还测量了血液、结肠和关节中 Th17/Treg 细胞的比例。应用代谢组学和 16S rRNA 测序来探讨肠道菌群和代谢物变化的影响：结果：GC 治疗组的关节病理学切片、炎症标志物和关节炎症指数评分与 CIA 组有显著差异。关于 GC 对肠道-关节轴影响的研究表明，脂多糖和二胺氧化酶的水平发生了变化，这两种物质都与肠道渗透性直接相关。当暴露于 GC 时，ZO-1、occludin 和 claudin-1 这三种肠道紧密连接蛋白的表达可能会增加。通过维持血液、结肠和关节中适当的 Th17/Treg 细胞比例，GC 可减少肠道屏障受损。肠道菌群和内源性物质的改变会导致肠道微环境失衡，从而损害肠道屏障。在 RA 治疗期间，GC 可通过修复肠道屏障来改变乳杆菌、梭菌、优杆菌、螺旋杆菌、普罗沃特斯菌和巴氏菌的相对丰度。代谢差异主要与初级胆汁酸生物合成、嘧啶代谢、类固醇生物合成、生物素代谢和鞘脂代谢有关。粪便微生物群移植实验证实，肠道微生物群及其代谢产物参与了 GC 介导的 RA 治疗：结果表明，GC 可修复肠道屏障，调整肠道-关节轴，从而控制 RA 的免疫失衡。

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Licorice-regulated gut-joint axis for alleviating collagen-induced rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is partially affected by the integrity of the intestinal barrier. Licorice (GC), a medicinal and food-related herb, exhibits potent anti-inflammatory activity; however, studies on its mechanisms of action in RA are limited.

Method: Using a bovine type-II collagen-induced arthritis rat model, this study examined how GC influences the gut-joint axis to decrease RA. The Th17/Treg cell ratios in the blood, colon, and joints were also measured. Metabolomics and 16S rRNA sequencing were applied to explore the effects of variations in gut flora and metabolites.

Results: The arthropathological slices, inflammation markers, and joint inflammation index scores in the GC treatment group significantly differed from those in the CIA group. Studies on the effect of GC on the gut-joint axis showed changes in the levels of lipopolysaccharide and diamine oxidase, both directly associated with intestinal permeability. ZO-1, occludin, and claudin-1, three intestinal tight-junction proteins, may express themselves more when exposed to GC. By maintaining an appropriate Th17/Treg cell ratio in the blood, colon, and joints, GC may reduce impaired to the intestinal barrier. An imbalance in the intestinal microenvironment, caused by modifications in gut flora and endogenous substances, can damage the intestinal barrier. GC may modify the relative abundances of Papillibacter, Clostridium, Eubacterium, Helicobacter, Provotella, and Barnesiella during RA treatment by repairing the intestinal barrier. The metabolic differences were mainly related to primary bile acid biosynthesis, pyrimidine metabolism, steroid biosynthesis, biotin metabolism, and sphingolipid metabolism. A fecal microbiota transplantation experiment confirmed the involvement of the gut microbiota and its metabolites in GC-mediated RA therapy.

Conclusion: The results demonstrated that GC repairs the intestinal barrier and adjusts the gut-joint axis to manage immunological imbalance in RA.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.