Kaneko Takao, Baba Naomichi, Matsuo Mitsuyoshi
Redox Regulation Research Group, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan.
Chem Biol Interact. 2003 Jan 6;142(3):239-54. doi: 10.1016/s0009-2797(02)00077-7.
Coumarins comprise a group of natural phenolic compounds found in a variety of plant sources. Protective effects of coumarins against cytotoxicity induced by linoleic acid hydroperoxide were examined in cultured human umbilical vein endothelial cells. When the cells were incubated in medium supplemented with linoleic acid hydroperoxide and coumarins, esculetin (6,7-dihydroxycoumarin) and 4-methylesculetin protected cells from injury by linoleic acid hydroperoxide. Fraxetin and caffeic acid showed weak, but significant, protection. Esculin as well as esculetin and 4-methylesculetin were effective for protecting cells against linoleic acid hydroperoxide-induced cytotoxicity in the case of pretreatment for 24 h, however fraxetin and caffeic acid showed no protection. Since esculetin was detected after 24 h treatment with esculin, a sugar moiety in the esculin molecule appears to be hydrolyzed during pretreatment. Coumarins such as umbelliferone containing only one hydroxyl group showed no protective effect in pretreatment or concurrent treatment. Esculetin and 4-methylesculetin provided synergistic protection against cytotoxicity induced by linoleic acid hydroperoxide with alpha-tocopherol. Furthermore, the radical-scavenging ability of coumarins was examined in electron spin resonance spectrometry. Esucletin, 4-methylesculetin, fraxetin, and caffeic acid showed the quenching effect on the 1,1-diphenyl-2-picrylhydrazyl radical. These results indicate that the presence of an ortho catechol moiety in the coumarin molecules plays an important role in the protective activities against linoleic acid hydroperoixde-induced cytotoxicity.
香豆素是一类存在于多种植物来源中的天然酚类化合物。在培养的人脐静脉内皮细胞中检测了香豆素对亚油酸氢过氧化物诱导的细胞毒性的保护作用。当细胞在补充有亚油酸氢过氧化物和香豆素的培养基中孵育时，七叶亭（6,7-二羟基香豆素）和4-甲基七叶亭可保护细胞免受亚油酸氢过氧化物的损伤。滨蓟黄素和咖啡酸显示出较弱但显著的保护作用。七叶苷以及七叶亭和4-甲基七叶亭在预处理24小时的情况下对保护细胞免受亚油酸氢过氧化物诱导的细胞毒性有效，然而滨蓟黄素和咖啡酸没有显示出保护作用。由于在用七叶苷处理24小时后检测到了七叶亭，七叶苷分子中的糖部分在预处理期间似乎被水解了。仅含有一个羟基的香豆素如伞形酮在预处理或同时处理中没有显示出保护作用。七叶亭和4-甲基七叶亭与α-生育酚对亚油酸氢过氧化物诱导的细胞毒性提供协同保护。此外，在电子自旋共振光谱法中检测了香豆素的自由基清除能力。七叶亭、4-甲基七叶亭、滨蓟黄素和咖啡酸对1,1-二苯基-2-苦基肼自由基显示出淬灭作用。这些结果表明香豆素分子中邻苯二酚部分的存在在对亚油酸氢过氧化物诱导的细胞毒性的保护活性中起重要作用。
