In patients with chronic kidney disease, the uremic toxin indoxyl sulfate (IS) accelerates kidney damage and the progression of cardiovascular disease. IS may contribute to vascular diseases by inducing inflammation in endothelial cells. Luteolin has documented antioxidant and anti‐inflammatory properties. This study aimed to investigate the effect of luteolin on IS‐mediated reactive oxygen species (ROS) production and intercellular adhesion molecule (ICAM‐1) and monocyte chemoattractant protein (MCP‐1) expression in EA.hy926 cells and the possible mechanisms involved. IS significantly induced ROS production (by 6.03‐fold, p < 0.05), ICAM‐1 (by 2.19‐fold, p < 0.05) and MCP‐1 protein expression (by 2.18‐fold, p < 0.05), and HL‐60 cell adhesion (by 31%, p < 0.05), whereas, luteolin significantly decreased IS‐induced ROS production, ICAM‐1 and MCP‐1 protein expression, and HL‐60 cell adhesion. Moreover, luteolin attenuated IS‐induced nuclear accumulation of p65 and c‐jun. Luteolin dose‐dependently increased heme oxygenase‐1 (HO‐1) expression and the maximum fold induction of HO‐1 by luteolin was 3.68‐fold (p < 0.05), whereas, HO‐1 knockdown abolished the suppression of ICAM‐1 and MCP‐1 expression by luteolin. Luteolin may protect against IS‐induced vessel damage by inducing HO‐1 expression in vascular endothelial cells, which suppresses nuclear factor kappa B (NF‐κB) and activator protein 1 (AP‐1) mediated ICAM‐1 and MCP‐1 expression.

中文翻译：

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木犀草素通过诱导 EA.hy926 人内皮细胞中 HO-1 的表达来抑制硫酸吲哚基诱导的 ICAM-1 和 MCP-1 表达


在慢性肾病患者中，尿毒症毒素硫酸吲哚酯 （IS） 会加速肾脏损伤和心血管疾病的进展。IS 可能通过诱导内皮细胞炎症而导致血管疾病。木犀草素具有抗氧化和抗炎特性。本研究旨在探讨木犀草素对 EA.hy926 细胞中 IS 介导的活性氧 （ROS） 产生和细胞间粘附分子 （ICAM-1） 和单核细胞趋化蛋白 （MCP-1） 表达的影响以及可能的机制。IS 显著诱导 ROS 产生 （6.03 倍，p < 0.05）、ICAM-1 （2.19 倍，p < 0.05） 和 MCP-1 蛋白表达 （2.18 倍，p < 0.05） 和 HL-60 细胞粘附 （31%，p < 0.05），而木犀草素显着降低 IS 诱导的 ROS 产生、ICAM-1 和 MCP-1 蛋白表达以及 HL-60 细胞粘附。此外，木犀草素减弱了 IS 诱导的 p65 和 c-jun 的核积累。木犀草素剂量依赖性地增加血红素加氧酶-1 （HO-1） 表达，木犀草素对 HO-1 的最大倍数诱导为 3.68 倍 （p < 0.05），而 HO-1 敲除消除了木犀草素对 ICAM-1 和 MCP-1 表达的抑制。木犀草素可以通过在血管内皮细胞中诱导 HO-1 表达来防止 IS 诱导的血管损伤，从而抑制核因子 kappa B （NF-κB） 和激活蛋白 1 （AP-1） 介导的 ICAM-1 和 MCP-1 表达。