Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.
Mol Nutr Food Res. 2014 May;58(5):1069-78. doi: 10.1002/mnfr.201300617. Epub 2014 Jan 10.
Oxidative stress-aggravated chronic inflammatory diseases of the airway are well documented; hence, treatment with antioxidants to ameliorate oxidative stress might be an effective strategy to reduce airway complications. The aim of this study was to investigate the effect and molecular mechanism of diallyl sulfide (DAS), which is a natural organosulfuric compound found in garlic, on the inhibition of tumor necrosis factor-alpha (TNF-α)- or histamine-induced inflammation in rat aortic smooth muscle A7r5 cells.
A7r5 cells were coincubated with DAS before exposure to TNF-α or histamine. DAS significantly blocked the accumulation of the nuclear p65 protein in TNF-α-induced A7r5 cells by attenuating the TNF-α receptor complex through the dissociation of the TNF receptor-associated death domain and TNF receptor-associated factor 2. Moreover, DAS inhibited histamine-induced inflammation by decreasing reactive oxygen species (ROS) levels by enhancing the nuclear factor-erythroid 2-related factor 2-related antioxidative enzyme. DAS also inhibited inflammation by suppressing interleukin-1β and TNF-α through the inhibition of ROS-induced PI3K/Akt and the downstream NF-κB and activator protein-1.
Our results demonstrate that DAS is a potential phytochemical to inhibit TNF-α- and histamine-induced inflammation, suggesting that DAS might be an effective dietary agent for the prevention of oxidative stress-induced inflammation of the airway.
氧化应激加重气道慢性炎症性疾病已有充分的文献记载;因此,用抗氧化剂来减轻氧化应激可能是减少气道并发症的有效策略。本研究的目的是研究大蒜中天然有机硫化合物二烯丙基二硫(DAS)抑制肿瘤坏死因子-α(TNF-α)或组胺诱导的大鼠主动脉平滑肌 A7r5 细胞炎症的作用和分子机制。
A7r5 细胞在暴露于 TNF-α或组胺之前与 DAS 共同孵育。DAS 通过 TNF 受体相关死亡结构域和 TNF 受体相关因子 2 的解离,减弱 TNF-α 受体复合物,从而显著阻断 TNF-α诱导的 A7r5 细胞中核 p65 蛋白的积累。此外,DAS 通过增强核因子-红细胞 2 相关因子 2 相关抗氧化酶来降低活性氧(ROS)水平,从而抑制组胺诱导的炎症。DAS 还通过抑制 ROS 诱导的 PI3K/Akt 和下游 NF-κB 和激活蛋白-1 来抑制炎症因子白细胞介素-1β和 TNF-α的表达。
我们的结果表明,DAS 是一种潜在的植物化学物质,可以抑制 TNF-α和组胺诱导的炎症,提示 DAS 可能是预防氧化应激诱导的气道炎症的有效膳食因子。