Anti-inflammatory effects of 4'-demethylnobiletin, a major metabolite of nobiletin.
Anti-inflammatory effects of 4'-demethylnobiletin, a major metabolite of nobiletin.
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DOI：
10.1016/j.jff.2015.09.035
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发表时间：
2015-12-01
影响因子：
5.6
通讯作者：
Xiao H
中科院分区：
文献类型：
--
作者：
Wu X;Song M;Rakariyatham K;Zheng J;Guo S;Tang Z;Zhou S;Xiao H
川陈皮素是一种柑橘类黄酮，具有多种有益的生物活性。 4′-去甲基川陈皮素（4DN）是川陈皮素的主要代谢产物，小鼠口服川陈皮素后，其组织水平远高于川陈皮素。在脂多糖 (LPS) 处理的 RAW 264.7 巨噬细胞中研究了 4DN 的抗炎作用。结果显示，4DN不仅剂量依赖性地抑制LPS诱导的一氧化氮产生，而且还显着降低促炎介质，即PGE2、IL-1β和IL-6的表达。 4DN 在蛋白质和 mRNA 水平上有效抑制 iNOS 和 COX-2 的表达。 4DN 还抑制 NF-κB 和 AP-1 的核转位。此外，我们证明4DN激活转录因子Nrf2及其依赖性基因，包括HO-1和NQO1，其表达可能有助于抗炎作用。结果证明了 4DN 的抗炎作用，并为使用川陈皮素作为营养保健品抑制炎症引起的疾病提供了科学依据。
Nobiletin, a citrus flavonoid has been associated with various beneficial biological activities. 4′-Demethylnobiletin (4DN) is a major metabolite of nobiletin and its tissue level was found to be much higher than that of nobiletin after oral administration of nobiletin in mice. Anti-inflammatory effects of 4DN were studied in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. The results showed 4DN not only dose-dependently inhibited LPS-induced nitric oxide production, but also significantly reduced expression of pro-inflammatory mediators, namely PGE2, IL-1β and IL-6. 4DN potently suppressed the expression of iNOS and COX-2 at both protein and mRNA levels. 4DN also inhibited nuclear translocation of NF-κB and AP-1. Furthermore, we demonstrated that 4DN activated transcription factor Nrf2 and its dependent genes including HO-1 and NQO1 whose expression may contribute to anti-inflammatory effects. The results demonstrated anti-inflammatory effects of 4DN and provided a scientific basis for using nobiletin as a nutraceutical to inhibit inflammation–driven diseases.