Tinosporine通过调节肠道微生物-代谢组-免疫轴减轻大鼠胶原诱导的关节炎

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-04-28 DOI:10.1016/j.intimp.2025.114752

Chuan Liu , Xiangrui Yi , Ping Wang , Peng Wang , Yafan Li , Huijuan Xu , Ling Li , WenYu Yang , Ya Tu

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引用次数: 0

摘要

背景类风湿性关节炎（RA）是一种炎症介导的自身免疫性疾病。Tinosporine (TIN)，源自Tinospora sinensis （Lour.）稳定。具有显著的抗炎和免疫抑制作用。然而，TIN的抗ra作用及其机制尚未完全阐明。目的基于肠道微生物-代谢-免疫轴，探讨TIN缓解大鼠胶原性关节炎（CIA）的作用机制。材料与方法建立CIA大鼠模型，评价TIN的作用。通过16S rRNA测序分析、粪便代谢组学分析和短链脂肪酸浓度测定，探讨TIN对肠道菌群组成和代谢组变化的影响。组织病理学结果显示TIN对肠道屏障有保护作用，采用ELISA和流式细胞术分析TIN的作用机制，并采用qRT-PCR和WB验证。结果TIN可改善CIA大鼠关节损伤和炎症反应，组织病理学观察证实TIN对肠道屏障有保护作用。16S rRNA测序分析和粪便代谢组学分析证实，TIN干预可调节肠道微生物组的组成，促进益生菌的繁殖，TIN干预可逆转CIA组12种血清代谢物的丰度变化。经TIN干预后，丙酸、丁酸、异丁酸、戊酸、异戊酸、己酸明显升高，但乙酸不能逆转。ELISA和流式细胞术证实，TIN干预可调节CIA大鼠结肠内炎症因子水平，维持肠屏障完整性，恢复结肠内Th1/Th2和Th17/Treg比例失衡。结论tin通过调节肠道微生物组-代谢组-免疫轴抑制CIA大鼠的炎症反应，逆转肠道菌群异常和差异代谢物，维持肠道屏障的完整性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Tinosporine alleviates collagen-induced arthritis in rats via modulating the gut microbiota-metabolome-immunity axis

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Tinosporine alleviates collagen-induced arthritis in rats via modulating the gut microbiota-metabolome-immunity axis

Background

Rheumatoid arthritis (RA) is an inflammation-mediated autoimmune disease. Tinosporine (TIN), derived from Tinospora sinensis (Lour.) Merr. has significant anti-inflammatory and immunosuppressive effects. However, the anti-RA effect and mechanism of TIN have not been fully elucidated.

Objective

This study elucidates the mechanism of TIN in alleviating collagen-induced arthritis (CIA) in rats based on the gut microbiome-metabolomic-immunity axis.

Materials and methods

We established CIA rat model to evaluate the efficacy of TIN. Based on 16S rRNA sequencing analysis, fecal metabolomics profiling and the concentrations of short-chain fatty acids determination to investigate the effect of TIN on gut microbiota composition and metabolome changes. Histopathology showed that TIN protected the intestinal barrier, then use ELISA and flow cytometry to analyze the mechanism of TIN, and qRT-PCR and WB were employed for verification.

Results

TIN ameliorated joint damage and inflammation in CIA rats, histopathological observation confirmed that TIN had protective effect on intestinal barrier. 16S rRNA sequencing analysis and fecal metabolomics profiling confirmed that TIN intervention regulates the composition of gut microbiome and promote the propagation of probiotics, the abundance changes of 12 serum metabolites in the CIA group were reversed by TIN intervention. After intervention with TIN, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, and caproic acid rise significantly, but acetic acid cannot be reversed. Then ELISA and flow cytometry confirmed that TIN intervention could regulate the level of inflammatory factors, maintain the integrity of the intestinal barrier and restoring the imbalance of Th1/Th2 and Th17/Treg ratios in the colon of CIA rats.

Conclusion

TIN inhibited the inflammatory response of CIA rats by regulating the gut microbiome-metabolome-immunity axis, reversed the abnormalities of intestinal flora and differential metabolites, and maintained the integrity of the intestinal barrier.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.