Kim K M, Chun S B, Koo M S, Choi W J, Kim T W, Kwon Y G, Chung H T, Billiar T R, Kim Y M
Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chunchon, Kangwon-do, South Korea.
Free Radic Biol Med. 2001 Apr 1;30(7):747-56. doi: 10.1016/s0891-5849(01)00460-9.
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 IFNgamma. 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-kappaB activation and murine iNOS promoter activity in LPS and IFNgamma-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 SAC, 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.
大蒜一直被用作预防和治疗心血管疾病的传统药物。然而，大蒜药理作用的分子机制尚未完全阐明。我们在此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一氧化氮（NO）生成的影响。本研究表明，这些试剂通过抑制脂多糖（LPS）和γ干扰素（IFNγ）刺激的小鼠巨噬细胞系RAW264.7中诱导型一氧化氮合酶（iNOS）的mRNA和蛋白表达来抑制NO生成。大蒜提取物还抑制了LPS加细胞因子刺激的腹膜巨噬细胞、大鼠肝细胞和大鼠主动脉平滑肌细胞中的NO生成，但不抑制iNOS转染的AKN - 1细胞中的NO生成或iNOS酶活性。这些试剂在LPS和IFNγ刺激的RAW264.7细胞中抑制核因子κB（NF - κB）激活和小鼠iNOS启动子活性。相反，这些试剂在人脐静脉内皮细胞（HUVEC）中显著增加了内皮型一氧化氮合酶（eNOS）介导的环磷酸鸟苷（cGMP）生成，而eNOS的活性、蛋白水平和细胞分布没有变化。最后，大蒜提取物和SAC均抑制羟自由基的产生，证实了它们的抗氧化活性。这些数据表明，大蒜提取物和SAC由于其抗氧化活性，通过抑制巨噬细胞中的iNOS表达同时增加内皮细胞中的NO生成来差异调节NO生成。因此，这种选择性调节可能有助于这些试剂的抗炎作用和动脉粥样硬化的预防。
