Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxygenase-2 and the induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 264.7 cells
Effect of wogonin, a plant flavone from Scutellaria radix, on the suppression of cyclooxygenase-2 and the induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 264.7 cells
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DOI：
10.1016/s0006-2952(01)00597-4
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发表时间：
2001-05-15
影响因子：
5.8
通讯作者：
Kim, HP
中科院分区：
文献类型：
--
作者：
Chi, YS;Cheon, BS;Kim, HP
植物黄酮类化合物在体外和体内均表现出抗炎活性。一些黄酮类化合物，如黄酮衍生物，已被报道通过抑制诱导型一氧化氮合酶（iNOS）的表达来抑制一氧化氮（NO）的产生。在这次调查中。使用小鼠巨噬细胞系RAW264.7，进一步阐明了汉黄芩素（在所测试的类黄酮中的一种有效的NO产生抑制剂）对环加氧酶-2（考克斯-2）诱导和活性的作用与iNOS的关系。汉黄芩素抑制脂多糖诱导的RAW细胞产生NO和前列腺素E-2（PGE（2）），IC 50值分别为31和0.3 μ M。当在诱导iNOS和考克斯-2后加入时。汉黄芩素抑制PGE（2）的形成（IC 50 = 0.8 μ M），但不抑制NO的产生。汉黄芩素直接抑制阿司匹林预处理的RAW细胞匀浆中的考克斯-2活性（IC 50 = 46 μ M），这通过测量[C-14]花生四烯酸形成[C-14]PGE（2）来确定。然而，它不抑制iNOS或磷脂酶A（2）的活性。Western blotting显示汉黄芩素抑制iNOS和考克斯-2的诱导。泼尼松龙还抑制iNOS和考克斯-2的诱导。而RU-486（类固醇受体拮抗剂）逆转泼尼松龙的抑制活性，它不影响汉黄芩素的抑制活性，这表明汉黄芩素的抑制活性不是通过结合类固醇受体介导的。本研究结果表明汉黄芩素是一种直接的考克斯-2抑制剂，同时也是诱导型一氧化氮合酶和考克斯-2诱导的抑制剂。汉黄芩素可能是一种潜在的治疗炎症性疾病的药物。(C)2001 Elsevier Science Inc. All rights reserved.
Plant flavonoids show anti-inflammatory activity both in vitro and in vivo. Some flavonoids, such as flavone derivatives, have been reported previously to inhibit nitric oxide (NO) production by suppressing inducible nitric oxide synthase (iNOS) expression. In this investigation. the effects of wogonin, a potent inhibitor of NO production among the flavonoids tested, on cyclooxygenase-2 (COX-2) induction and activity were elucidated further in connection with iNOS, using a mouse macrophage cell line, RAW 264.7. Wogonin inhibited NO and prostaglandin E-2 (PGE(2)) production from lipopolysaccharide-induced RAW cells with IC50 values of 31 and 0.3 muM, respectively. When added after the induction of iNOS and COX-2. wogonin inhibited the formation of PGE(2) (IC50 = 0.8 muM), but not the production of NO. Wogonin inhibited COX-2 activity directly (IC50 = 46 muM) from the homogenate of aspirin-pretreated RAW cells, as determined by measuring [C-14]PGE(2) formation from [C-14]arachidonic acid. However, it did not inhibit iNOS or phospholipase A(2) activity. Western blotting showed that wogonin suppressed the induction of both iNOS and COX-2. Prednisolone also suppressed the induction of iNOS and COX-2. Whereas RU-486 (a steroid receptor antagonist) reversed the suppressive activity of prednisolone, it did not affect the suppressive activity of wogonin, suggesting that the suppressive activity of wogonin is not mediated by binding to a steroid receptor. Results from the present study demonstrated that wogonin is a direct COX-2 inhibitor, as well as an inhibitor of iNOS and COX-2 induction. Wogonin may be a potential agent for use in the treatment of inflammatory diseases. (C) 2001 Elsevier Science Inc. All rights reserved.