Anti-Inflammatory Property of 5-Demethylnobiletin (5-Hydroxy-6, 7, 8, 3', 4'-pentamethoxyflavone) and Its Metabolites in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells.
Anti-Inflammatory Property of 5-Demethylnobiletin (5-Hydroxy-6, 7, 8, 3', 4'-pentamethoxyflavone) and Its Metabolites in Lipopolysaccharide (LPS)-Induced RAW 264.7 Cells.
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5-Demethylnobiletin (5-羟基-6,7,8,3',4'-五甲氧基黄酮, 5DN) 是一种生物活性多甲氧基黄酮，主要存在于柑橘类植物中。据我们所知，本研究是首次报道 5DN 及其代谢物对 RAW 264.7 巨噬细胞中 LPS 诱导的炎症的抑制机制。重要的是，5DN 的代谢物表现出比母体化合物更有效的活性。 5DN及其代谢物的结构特性与其抗炎活性之间可能的关系值得进一步研究。羟基化多甲氧基黄酮 (PMF) 是一类独特的黄酮类化合物，主要存在于柑橘类植物中。我们研究了一种主要的 5-羟基 PMF，即 5-去甲基川陈皮素 (5DN) 及其代谢物 5, 3'-二去甲基川陈皮素 (M1)、5, 4'-二去甲基川陈皮素 (M2) 和 5, 3', 4'-三去甲基川陈皮素 (M3) 在脂多糖 (LPS) 刺激的 RAW 264.7 中的抗炎作用巨噬细胞。结果表明，在非细胞毒性浓度下，M2和M3对一氧化氮（NO）产生的抑制作用比其母体化合物更强。 Western blotting 和实时 PCR 分析表明，M2 和 M3 显着降低 iNOS 和 COX-2 基因表达。结果还表明M1和M3诱导血红素加氧酶1(HO-1)基因表达。总体而言，我们的结果表明，5DN 的代谢物显着抑制 RAW 264.7 巨噬细胞中 LPS 诱导的炎症，并且通常比母体化合物 5DN 具有更有效的抗炎活性。
5-Demethylnobiletin (5-hydroxy-6, 7, 8, 3′, 4′-pentamethoxyflavone, 5DN) is a bioactive polymethoxyflavone mainly found in citrus plants. To our knowledge, the present study is the first report on the inhibitory mechanism of 5DN and its metabolites on LPS-induced inflammation in RAW 264.7 macrophage cells. Importantly, 5DN’s metabolites showed more potent activities than the parent compound. The possible relationship between the structural properties of 5DN and its metabolites and their anti-inflammatory activity deserves further investigation. Hydroxylated polymethoxyflavones (PMFs) are a unique class of flavonoid compounds mainly found in citrus plants. We investigated the anti-inflammatory effects of one major 5-hydroxy PMF, namely 5-demethylnobiletin (5DN) and its metabolites 5, 3′-didemethylnobiletin (M1), 5, 4′-didemethylnobiletin (M2), and 5, 3′, 4′-tridemethylnobiletin (M3) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The results showed that M2 and M3 produced stronger inhibitory effects on the production of nitric oxide (NO) than their parent compound at non-cytotoxic concentrations. Western blotting and real-time PCR analyses demonstrated that M2 and M3 significantly decreased iNOS and COX-2 gene expression. The results also showed that M1 and M3 induced heme oxygenase-1(HO-1) gene expression. Overall, our results demonstrated that metabolites of 5DN significantly inhibited LPS-induced inflammation in RAW 264.7 macrophage cells and generally possessed more potent anti-inflammatory activity than the parent compound, 5DN.
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影响因子：
2.7
作者：
Li, Shiming;Sang, Shengmin;Ho, Chi-Tang
通讯作者：
Ho, Chi-Tang
影响因子：
4.8
作者：
Lee, TS;Tsai, HL;Chau, LY
通讯作者：
Chau, LY
影响因子：
6.1
作者：
Li, Shiming;Lo, Chih-Yu;Ho, Chi-Tang
通讯作者：
Ho, Chi-Tang
影响因子：
4.3
作者：
Kim, Hana;Moon, Jeong Yong;Cho, Somi Kim
通讯作者：
Cho, Somi Kim
DOI：
10.1016/j.jchromb.2006.09.010
发表时间：
2007-02-01
影响因子：
3
作者：
Li, Shiming;Lambros, Ted;Ho, Chi-Tang
通讯作者：
Ho, Chi-Tang