Jinwu Jiangu capsule attenuates rheumatoid arthritis via the SLC7A11/GSH/GPX4 pathway in M1 macrophages

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2024-11-15 DOI:10.1016/j.phymed.2024.156232

Yi Ling , Yuzheng Yang , Nina Ren , Hui Xu, Changming Cheng, Daomin Lu, Qiuyi Wang, Xueming Yao, Wukai Ma

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Abstract

Background

JinWu JianGu capsule (JWJGC) is a Chinese herbal medicine that alleviates the clinical manifestations of rheumatoid arthritis (RA). However, the mechanism of action requires further investigation..

Purpose

This study aimed to investigate the anti-inflammatory effects of JWJGC on RA via the regulation of reactive oxygen species (ROS) and ferroptosis.

Materials and methods

JWJGC was administered to rats with collagen-induced arthritis (CIA) via oral gavage for 28 days. In vitro, M1 macrophages were pre-treated with JWJGC-containing serum. After assessing joint swelling and physiologic, the M1/M2 macrophage ratio was detected in CIA rats. The levels of ROS markers were assessed in the serum and cell supernatants. Liquid chromatography-tandem mass spectrometry analyses were employed to check lipid metabolism, and changes in mitochondrial morphology during ferroptosis were detected by transmission electron microscopy. Western blotting, immunofluorescence, immunohistochemistry, and qRT-PCR were performed to validate these results.

Results

JWJGC ameliorated CIA by reducing ROS levels in rats. It also restored the balance of the M1/M2 macrophage ratio and reduced the levels of macrophage-related inflammatory markers. Additionally, JWJGC affected lipid metabolism to alleviate inflammation by downregulating lipids associated with ferroptosis. It attenuated ferroptosis by modulating glutathione (GSH)/ Glutathione peroxidase 4(GPX4) expression in CIA rats. In vitro, JWJGC targeted M1 macrophages via the solute carrier family 7a member 11 (SLC7A11)/GSH/GPX4 signaling pathway.

Conclusions

This study showed that JWJGC improved RA, primarily through the integrated regulation of the SLC7A11/GSH/GPX4 pathway in M1 macrophages. These findings provide an innovative therapeutic basis for RA treatment and expanding the clinical applications of JWJGC.

Abstract Image

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金乌健骨胶囊通过 M1 巨噬细胞中的 SLC7A11/GSH/GPX4 通路减轻类风湿性关节炎。

背景：金乌健骨胶囊（JWJGC）是一种中药，可缓解类风湿性关节炎（RA）的临床表现。目的：本研究旨在探讨金乌健骨胶囊通过调节活性氧（ROS）和铁蛋白沉积对 RA 的抗炎作用：通过口服给胶原诱导性关节炎（CIA）大鼠灌胃 JWJGC 28 天。在体外，用含有 JWJGC 的血清预处理 M1 巨噬细胞。在评估关节肿胀和生理状况后，检测 CIA 大鼠的 M1/M2 巨噬细胞比率。对血清和细胞上清液中的 ROS 标记水平进行了评估。采用液相色谱-串联质谱分析检测脂质代谢，并通过透射电子显微镜检测铁变态反应过程中线粒体形态的变化。为验证这些结果，还进行了 Western 印迹、免疫荧光、免疫组织化学和 qRT-PCR 分析：结果：JWJGC 通过降低 ROS 水平改善了大鼠的 CIA。结果：JWJGC 通过降低 ROS 水平改善了大鼠的 CIA，还恢复了巨噬细胞 M1/M2 比率的平衡，降低了巨噬细胞相关炎症标志物的水平。此外，JWJGC 还能影响脂质代谢，通过下调与铁变态反应相关的脂质来缓解炎症。它通过调节 CIA 大鼠体内谷胱甘肽（GSH）/谷胱甘肽过氧化物酶 4（GPX4）的表达，减轻了铁变态反应。在体外，JWJGC通过溶质运载家族7a成员11（SLC7A11）/GSH/GPX4信号通路靶向M1巨噬细胞：本研究表明，JWJGC 主要通过综合调节 M1 巨噬细胞中的 SLC7A11/GSH/GPX4 通路来改善 RA。这些发现为治疗 RA 提供了创新的治疗基础，并拓展了 JWJGC 的临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.