Zhejiang Chinese Medical University, Hangzhou, China.
Anat Rec (Hoboken). 2010 Mar;293(3):421-30. doi: 10.1002/ar.21070.
Garlic and its water-soluble allyl sulfur-containing compound, S-Allyl-L-cysteine Sulfoxide (ACSO), have shown antioxidant and anti-inflammatory activities, inhibiting the development of atherosclerosis. However, little is known about the mechanism(s) underlying the therapeutic effect of ACSO in inhibiting the formation of atherosclerostic lesion. This study aimed to investigate whether ACSO could modulate tumor necrosis factor-alpha (TNF-alpha)-induced expression of intercellular cell adhesion molecule-1, monocyte adhesion and TNF-alpha-mediated signaling in human umbilical vein endothelial cells. While TNF-alpha promoted the intercellular cell adhesion molecule-1 mRNA transcription in a dose- and time-dependent manner, ACSO treatment significantly reduced the levels of TNF-alpha-induced intercellular cell adhesion molecule-1 mRNA transcripts (P < 0.01). Furthermore, ACSO dramatically inhibited TNF-alpha triggered adhesion of THP-1 monocytes to endothelial cells and porcine coronary artery rings. Moreover, ACSO mitigated TNF-alpha induced depolarization of mitochondrial membrane potential and overproduction of superoxide anion, associated with the inhibition of NOX4, a subunit of nicotinamide adenine dinucleotide phosphate-oxidase, mRNA transcription. In addition, ACSO also inhibited TNF-alpha-induced phosphorylation of JNK, ERK1/2 and IkappaB, but not p38. Apparently, ACSO inhibited proinflammatory cytokine-induced adhesion of monocytes to endothelial cells by inhibiting the mitogen-activated protein kinase signaling and related intercellular cell adhesion molecule-1 expression, maintaining mitochondrial membrane potential, and suppressing the overproduction of superoxide anion in endothelial cells. Therefore, our findings may provide new insights into ACSO on controlling TNF-alpha-mediated inflammation and vascular disease.
大蒜及其水溶性烯丙基含硫化合物，S-烯丙基-L-半胱氨酸亚砜（ACSO），具有抗氧化和抗炎活性，可抑制动脉粥样硬化的发展。然而，关于 ACSO 抑制动脉粥样硬化病变形成的治疗作用的机制知之甚少。本研究旨在探讨 ACSO 是否可以调节肿瘤坏死因子-α（TNF-α）诱导的人脐静脉内皮细胞细胞间黏附分子-1、单核细胞黏附和 TNF-α介导的信号转导的表达。虽然 TNF-α以剂量和时间依赖的方式促进细胞间黏附分子-1 mRNA 的转录，但 ACSO 处理显著降低了 TNF-α诱导的细胞间黏附分子-1 mRNA 转录本的水平（P < 0.01）。此外，ACSO 可显著抑制 TNF-α触发的 THP-1 单核细胞与内皮细胞和猪冠状动脉环的黏附。此外，ACSO 减轻了 TNF-α诱导的线粒体膜电位去极化和超氧阴离子的过度产生，与烟酰胺腺嘌呤二核苷酸磷酸氧化酶的一个亚基 NOX4 的抑制有关，即转录。此外，ACSO 还抑制了 TNF-α诱导的 JNK、ERK1/2 和 IkappaB 的磷酸化，但不抑制 p38。显然，ACSO 通过抑制丝裂原活化蛋白激酶信号转导和相关的细胞间黏附分子-1 表达、维持线粒体膜电位以及抑制内皮细胞中超氧阴离子的过度产生，抑制促炎细胞因子诱导的单核细胞与内皮细胞的黏附。因此，我们的研究结果可能为 ACSO 控制 TNF-α 介导的炎症和血管疾病提供新的见解。
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