木兰脂素通过抑制 ALOX5 介导的铁蛋白沉积缓解了 DSS 诱导的结肠炎。

The Kaohsiung journal of medical sciences Pub Date : 2024-04-01 Epub Date: 2024-02-10 DOI:10.1002/kjm2.12806
Ting Yao, Yuan-Yuan Yao, Jin-Zhi Wang, Shi-Man Jiang, Lan-Juan Li
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引用次数: 0

摘要

炎症性肠病(IBD)是一种慢性不治之症,具有较高的癌症风险,目前的治疗效果并不理想。铁锈色细胞分泌的损伤相关分子模式(DAMPs)可招募并激活免疫细胞,尤其是巨噬细胞。木兰脂素具有很好的抗氧化和抗炎特性,但其对 IBD 的影响尚未得到明确了解。本研究旨在探讨木兰脂素对 IBD 的治疗作用和机制。为此,研究人员使用葡聚糖硫酸钠(DSS)建立了体内和体外结肠炎模型,并优化了镁磷脂在体外2.5 μg/mL和在体内5 mg/kg的浓度。生物信息学分析确定了潜在的magnolin靶点,并评估了铁蛋白沉积相关基因的表达。对体重、食物摄入量、疾病活动指数(DAI)、病理变化和炎症水平进行了评估。使用定量实时聚合酶链反应(qRT-PCR)、免疫荧光染色、流式细胞术、酶联免疫吸附试验(ELISA)和免疫印迹法评估了magnolin对铁蛋白沉积和巨噬细胞的影响。结果表明,较低剂量(5 毫克/千克)的 magnolin 可减轻 DSS 诱导的小鼠结肠炎症状并减轻炎症反应。生物信息学分析表明,花生四烯酸 5-脂氧合酶(ALOX5)是 magnolin 的潜在靶点。此外,magnolin 能抑制 ALOX5 的表达,而对 GPX4 没有影响。此外,magnolin 还能调节巨噬细胞向 M2 表型分化,并抑制促炎因子,即白细胞介素-6 和肿瘤坏死因子-α(IL-6 和 TNFα)。这些结果表明,magnolin通过抑制ALOX5介导的铁变态反应、抑制M1同时促进M2巨噬细胞,在治疗IBD方面具有显著的治疗潜力,有望为治疗IBD提供新的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Magnolin alleviated DSS-induced colitis by inhibiting ALOX5-mediated ferroptosis.

Inflammatory bowel disease (IBD) is a chronic and incurable disorder associated with higher cancer risk and currently faces unsatisfactory treatment outcomes. Ferroptotic cells secrete damage-associated molecular patterns (DAMPs) that recruit and activate immune cells, particularly macrophages. Magnolin has excellent antioxidant and anti-inflammatory properties, but its effect on IBD has not yet been clearly understood. This study aimed to investigate the therapeutic effects and mechanism of magnolin in IBD. For this purpose, in vivo and in vitro colitis models were established using dextran sulfate sodium (DSS), followed by optimization of magnolin concentration 2.5 μg/mL in vitro and 5 mg/kg in vivo. Bioinformatics analysis identified potential magnolin target sites and evaluated ferroptosis-associated gene expressions. Body weight, food intake, disease activity index (DAI), pathological changes, and inflammation levels were assessed. The effect of magnolin on ferroptosis and macrophages was evaluated using quantitative real time-polymerase chain reaction (qRT-PCR), immunofluorescent staining, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and western blotting. Results indicated that magnolin at a lower dose (5 mg/kg) alleviated DSS-induced colitis symptoms and reduced inflammation in mice. The bioinformatics analysis showed arachidonate 5-lipoxygenase (ALOX5) as a potential magnolin target. Furthermore, magnolin inhibited the expression of ALOX5 with no effect on GPX4. Moreover, magnolin regulated macrophage differentiation into the M2 phenotype and suppressed pro-inflammatory factors, that is, interleukin-6 and tumor necrosis factor-α (IL-6 and TNFα). These results suggested that magnolin possesses significant therapeutic potential in treating IBD by suppressing ALOX5-mediated ferroptosis, inhibiting M1 while promoting M2 macrophages, which is envisaged to provide novel strategies for treating IBD.

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