Guizhou University of Traditional Chinese Medicine, Guiyang, 550000, China.
Guizhou University of Traditional Chinese Medicine, Guiyang, 550000, China.
Phytomedicine. 2024 Dec;135:156232. doi: 10.1016/j.phymed.2024.156232. Epub 2024 Nov 15.
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..
This study aimed to investigate the anti-inflammatory effects of JWJGC on RA via the regulation of reactive oxygen species (ROS) and ferroptosis.
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.
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.
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.
金乌健骨胶囊（JWJGC）是一种缓解类风湿性关节炎（RA）临床表现的中草药。然而，其作用机制需要进一步研究。
本研究旨在通过调节活性氧（ROS）和铁死亡来研究 JWJGC 对 RA 的抗炎作用。
通过口服灌胃，JWJGC 给胶原诱导性关节炎（CIA）大鼠给药 28 天。体外，用 JWJGC 含血清预处理 M1 巨噬细胞。在评估关节肿胀和生理后，检测 CIA 大鼠中的 M1/M2 巨噬细胞比例。评估血清和细胞上清液中的 ROS 标志物水平。采用液相色谱-串联质谱分析检查脂质代谢，通过透射电子显微镜检测铁死亡过程中线粒体形态的变化。通过 Western blot、免疫荧光、免疫组化和 qRT-PCR 验证这些结果。
JWJGC 通过降低大鼠体内 ROS 水平改善 CIA。它还恢复了 M1/M2 巨噬细胞比例的平衡，并降低了巨噬细胞相关炎症标志物的水平。此外，JWJGC 通过下调与铁死亡相关的脂质来影响脂质代谢以减轻炎症。它通过调节 CIA 大鼠中的谷胱甘肽（GSH）/谷胱甘肽过氧化物酶 4（GPX4）表达来减轻铁死亡。在体外，JWJGC 通过溶质载体家族 7 成员 11（SLC7A11）/GSH/GPX4 信号通路靶向 M1 巨噬细胞。
本研究表明，JWJGC 通过调节 M1 巨噬细胞中的 SLC7A11/GSH/GPX4 通路改善 RA，为 RA 的治疗提供了新的治疗基础，并扩大了 JWJGC 的临床应用。
