Inhibition of the transcription factor NF-κB by sesquiterpene lactones from Podachaenium eminens
Inhibition of the transcription factor NF-κB by sesquiterpene lactones from Podachaenium eminens
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DOI：
10.1055/s-2000-8649
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发表时间：
2000-10-01
期刊：
影响因子：
2.7
通讯作者：
Merfort, I
中科院分区：
文献类型：
--
作者：
Castro, V;Murillo, R;Merfort, I
对 Podachaenium eminens 的研究提供了 9 种倍半萜内酯 (Sls)，其中木香烯内酯、7-羟基木香烯内酯、檀香素以及 3-氯脱氢白蛋白是该植物中的新化合物，并且 3,4-脱氢-4-脱氢白蛋白 (= 3-木香酰氧基脱氢白蛋白) 是在自然界中首次发现的。使用转录因子 NF-kappaB 作为分子靶标，研究了所有分离的 Sis 的抗炎活性。 NF-kappaB 参与炎症介质的合成，例如细胞因子和趋化因子。除 podachaenin 外，所有化合物在电泳迁移率变动测定中，浓度在 5 至 200 muM 之间时均完全抑制 NF-kappaB DNA 结合，且未显示任何细胞毒性作用。具有α-亚甲基-γ-丁内酯和通过其环氧环α,β到羰基的第二反应性结构元素的3,4-环氧脱氢亮古丁是最活跃的。尽管本研究中测试的大多数 Sis 都是单功能的，但通常仅需要 50 μM 的低浓度即可完全抑制。讨论了造成这一结果的可能原因。
Investigation of Podachaenium eminens afforded nine sesquiterpene lactones (Sls) from which costunolide, 7-hydroxycostunolide, santamarin as well as 3-chlorodehydroleucodin are new for this plant and 3,4-dehydro-4-dehydroxypodachaenin (= 3-costoyloxydehydroleucodin) is found for the first time in nature. All isolated Sis were studied for their anti-inflammatory activity using the transcription factor NF-kappaB as a molecular target. NF-kappaB is involved in the synthesis of inflammatory mediators, such as cytokines and chemokines. Except for podachaenin, all compounds completely inhibited NF-kappaB DNA binding in an electrophoretic mobility shift assay at concentrations between 5 and 200 muM without showing any cytotoxic effects. 3,4-Epoxydehydroleucodin possessing an alpha -methylene-gamma -butyrolactone and a second reactive structure element by its epoxy ring alpha,beta to a carbonyl group was most active. Although the majority of the Sis tested in this study were monofunctional only low concentrations of 50 muM were often needed for complete inhibition. Possible reasons are discussed for this result.