大蒜及其有機硫化物抑制一氧化氮生合成之探討

中山醫學大學機構典藏 CSMUIR > 健康管理學院 > 營養學系暨碩士班 > 研究計劃 > Item 310902500/2789

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/2789

Title:	大蒜及其有機硫化物抑制一氧化氮生合成之探討 The Effect of Garlic and Its Organosulfur Compounds on Lipopolysaccharide-Induced No Production
Authors:	李宗貴;王瑞筠;雷燕萍 Lii, Chong-Kuei;Wang, Ruei-Yun
Contributors:	中山醫學院營養學系
Keywords:	大蒜;有機硫成分;一氧化氮;誘導型一氧化氮合成脢 garlic;organosulfur compounds;nitric oxide;inducible nitric oxide synthase
Date:	2004
Issue Date:	2010-11-24T07:49:36Z (UTC)
Abstract:	動脈粥狀硬化的發生與不當或長期慢性的發炎反應有關，在發炎狀態下，會導致活化的巨噬細胞或肥大細胞釋放大量NO、細胞激素或PGE2等發炎因子，因此，減少NO或其他發炎因子的生成，應有助於抑制發炎反應，而能預防、改善心血管疾病。雖已有研究證實大蒜及其組成分具有調控發炎反應，進而抗動脈粥狀硬化與心血管疾病之生理效用，然而有關大蒜脂溶性有機硫化物於此方面的研究尚少，故本實驗以diallyl sulfide (DAS)、diallyl disulfide (DADS)與diallyl trisulfide (DATS)三種各差一個硫原子的脂溶性大蒜有機硫化物為主要研究材料，探討它們在LPS誘發RAW264.7巨噬細胞發炎反應下，調控iNOS表現之效應，及其上游轉錄因子—NF-κB在其中扮演之角色，並將其作用與另兩種水溶性硫化物—S-allyl cysteine (SAC)與N-acetyl-cysteine (NAC)之效應作比較。結果顯示，在1μg/ml LPS誘發發炎反應下，MTT分析指出100-1000μM DAS、50-400μM DADS、25-200μM DATS、1-10μM SAC或NAC並不影響細胞存活率。在NO生成與iNOS表現效應方面，DAS並無抑制NO生成與iNOS表現之作用，SAC或NAC僅在10mM處理濃度下方能降低NO生成與iNOS蛋白質表現；然而，DADS與DATS則明顯在抑制LPS活化iNOS蛋白質與mRNA表現上有較強效應，因而抑制NO生合成之效應也顯著高於DAS、NAC與SAC。進一步探討DADS與DATS抑制發炎反應與上游轉錄因子—NF-κB的活化關係，結果也發現，DADS與DATS抑制iNOS表現確實與NF-κB轉錄因子活性受到抑制有關。由於DADS與DATS是大蒜精油中含量最多之硫成分，因此，本研究推論大蒜精油或許具有發展為抗發炎健康食品，進而改善或預防心血管疾病之潛能。 Atherosclerosis is a chronic inflammatory disease affecting arterial vessels. In atherosclerosis lesions, inflammatory processes upregulate iNOS expression in macrophages, resulting in excessive nitric oxide (NO) production and vascular damage. Thus, suppression of NO production, via inhibition of iNOS expression and/or activity, is an attractive therapeutic target for the treatment of cardiovascular diseases. Garlic has been used as a traditional medicine for prevention and treatment of cardiovascular diseases. However, the effect of lipid-soluble organosulfur compounds derived from garlic has not been clearly elucidated. The aim of this study was to investigate the inhibition of diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) on iNOS expression and NF-kappaB activation in lipopolysacchareide (LPS)-stimulated RAW264.7 macrophages and compared the effect with two water soluble organosulfur compounds, i.e. S-allyl cysteine (SAC) and N-acetyl-cysteine (NAC). LPS-activated RAW264.7 cells were treated with 100-1000 microM DAS, 50-400 microM DADS, 25-200 microM DATS, 1-10 mM SAC or NAC, respectively, which did not reduce cell viability as measured by MTT assay. DAS did not affect NO production and iNOS expression. SAC or NAC at only 10 mM inhibited NO production and iNOS protein levels. In contrast, DADS and DATS showed more inhibitory potential at NO, iNOS protein and mRNA levels. By gel electrophoresis mobility shift assy, DADS and DATS were effective in the inhibition of NF-kappaB activation. Results suggest that DADS and DATS, the two major organosulfur compounds of garlic, could be important in modulating the NF-kappaB-related health impact.
URI:	https://ir.csmu.edu.tw:8080/handle/310902500/2789
Appears in Collections:	[營養學系暨碩士班] 研究計劃

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