Lu H W, Sugahara K, Sagara Y, Masuoka N, Asaka Y, Manabe M, Kodama H
Department of Anesthesia, Kochi Medical School, Kohasu, Kochi, 783-8505, Japan.
Arch Biochem Biophys. 2001 Sep 1;393(1):73-7. doi: 10.1006/abbi.2001.2457.
The effect of three flavonoids, 5,7,3',4'-tetrahydoxy-3-methoxy flavone (THMF), luteolin, and quercetin, on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophils were investigated. When the cells were preincubated with these flavonoids, the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was significantly suppressed, showing a dependence on amounts of the flavonoid. The suppressing effect of the flavonoid was THMF > luteolin > quercetin. These flavonoids also suppressed the superoxide generation induced by phorbol 12-myristate 13-acetate. In this case also, THMF was more effective than luteolin and quercetin. On the other hand, the superoxide generation induced by arachidonic acid was markedly suppressed by quercetin. The suppressing effect was quercetin >> THMF > luteolin. THMF, luteolin, and quercetin significantly suppressed tyrosyl phosphorylation of 80.1-, 58.0-, and 45.0-kDa proteins in fMLP-treated human neutrophils. The suppression depended on the concentration of the flavonoids, and the inhibition of tyrosyl phosphorylation was in parallel to that of the fMLP-induced superoxide generation, respectively. While luteolin and quercetin showed a weak hemolytic activity at 2.5 mM, THMF showed almost no hemolytic activity even at 5 mM, suggesting an advantage of THMF for its clinical use.
研究了三种黄酮类化合物，即5,7,3',4'-四羟基-3-甲氧基黄酮（THMF）、木犀草素和槲皮素，对人中性粒细胞中刺激诱导的超氧化物生成及蛋白质酪氨酸磷酸化的影响。当细胞与这些黄酮类化合物预孵育时，N-甲酰甲硫氨酰亮氨酰苯丙氨酸（fMLP）诱导的超氧化物生成受到显著抑制，且呈黄酮类化合物剂量依赖性。黄酮类化合物的抑制作用为THMF＞木犀草素＞槲皮素。这些黄酮类化合物还抑制了佛波酯12-肉豆蔻酸酯13-乙酸酯诱导的超氧化物生成。在这种情况下，THMF也比木犀草素和槲皮素更有效。另一方面，槲皮素显著抑制了花生四烯酸诱导的超氧化物生成。抑制作用为槲皮素＞＞THMF＞木犀草素。THMF、木犀草素和槲皮素显著抑制了fMLP处理的人中性粒细胞中80.1 kDa（千道尔顿）、58.0 kDa和45.0 kDa蛋白质的酪氨酸磷酸化。这种抑制作用取决于黄酮类化合物的浓度，并且酪氨酸磷酸化的抑制分别与fMLP诱导的超氧化物生成的抑制作用平行。虽然木犀草素和槲皮素在2.5 mM时表现出较弱的溶血活性，但THMF即使在5 mM时也几乎没有溶血活性，这表明THMF在临床应用方面具有优势。
