Differential regulation of NO availability from macrophages and endothelial cells by the garlic component S-allyl cysteine
Differential regulation of NO availability from macrophages and endothelial cells by the garlic component S-allyl cysteine
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DOI：
10.1016/s0891-5849(01)00460-9
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发表时间：
2001-04-01
影响因子：
7.4
通讯作者：
Kim, YM
中科院分区：
文献类型：
--
作者：
Kim, KM;Chun, SB;Kim, YM
大蒜一直被用作预防和治疗心血管疾病的传统药物。然而，大蒜的药理作用的分子机制尚未明确阐明。我们研究了大蒜提取物及其主要成分S-烯丙基半胱氨酸（SAC）对巨噬细胞和内皮细胞产生一氧化氮（NO）的影响。本研究表明，这些试剂通过抑制小鼠巨噬细胞系RAW 264.7中的iNOS mRNA和蛋白质表达来抑制NO的产生，所述巨噬细胞系RAW 264.7已被LPS和IFN γ刺激。大蒜提取物也抑制NO的产生在腹腔巨噬细胞，大鼠肝细胞，大鼠主动脉平滑肌细胞刺激LPS加细胞因子，但它不抑制NO的产生在iNOS转染的AKN-1细胞或iNOS酶活性。这些试剂抑制LPS和IFN γ刺激的RAW 264.7细胞中的NF-κ B活化和鼠iNOS启动子活性。与此相反，这些试剂显着增加cGMP的生产eNOS在HUVEC的活性，蛋白水平和eNOS的细胞分布没有变化。最后，大蒜提取物和SAC都抑制了羟基自由基的产生，证实了它们的抗氧化活性。这些数据表明，大蒜提取物和SAG，由于它们的抗氧化活性，差异调节NO的产生，抑制iNOS在巨噬细胞的表达，同时增加NO在内皮细胞。因此，这种选择性调节可能有助于这些试剂的抗炎作用和预防动脉粥样硬化。(C)2001 Elsevier Science Inc.
Garlic has been used as a traditional medicine for prevention and treatment of cardiovascular diseases. However, the molecular mechanism of garlic's pharmacological action has not been clearly elucidated. We examined here the effect of garlic extract and its major component, S-allyl cysteine (SAC), on nitric oxide (NO) production by macrophages and endothelial cells. The present study demonstrates that these reagents inhibited NO production through the suppression of iNOS mRNA and protein expression in the murine macrophage cell line RAW264.7, which had been stimulated with LPS and IFN gamma. The garlic extract also inhibited NO production in peritoneal macrophages, rat hepatocytes, and rat aortic smooth muscle cells stimulated with LPS plus cytokines, but it did not inhibit NO production in iNOS-transfected AKN-1 cells or iNOS enzyme activity. These reagents suppressed NF-KB activation and murine iNOS promoter activity in LPS and IFN gamma -stimulated RAW264.7 cells. In contrast, these reagents significantly increased cGMP production by eNOS in HUVEC without changes in activity, protein levels, and cellular distribution of eNOS. Finally, garlic extract and SAC both suppressed the production of hydroxyl radical, confirming their antioxidant activity. These data demonstrate that garlic extract and SAG, due to their antioxidant activity, differentially regulate NO production by inhibiting iNOS expression in macrophages while increasing NO in endothelial cells. Thus, this selective regulation may contribute to the anti-inflammatory effect and prevention of atherosclerosis by these reagents. (C) 2001 Elsevier Science Inc.