Inhibitory effects of benzaldehyde derivatives from the marine fungus Eurotium sp. SF-5989 on inflammatory mediators via the induction of heme oxygenase-1 in lipopolysaccharide-stimulated RAW264.7 macrophages.
Inhibitory effects of benzaldehyde derivatives from the marine fungus Eurotium sp. SF-5989 on inflammatory mediators via the induction of heme oxygenase-1 in lipopolysaccharide-stimulated RAW264.7 macrophages.
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DOI：
10.3390/ijms151223749
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发表时间：
2014-12-19
影响因子：
5.6
通讯作者：
Oh H
中科院分区：
文献类型：
--
作者：
Kim KS;Cui X;Lee DS;Ko W;Sohn JH;Yim JH;An RB;Kim YC;Oh H
从海洋真菌散囊菌 (Eurotium sp.) 中分离出两种苯甲醛衍生物，黄酮亮星 (1) 和异四氢金亮星 (2)。 SF-5989 通过生物测定和 1H NMR 引导的研究。在这项研究中，我们评估了这些化合物在脂多糖 (LPS) 刺激的 RAW264.7 巨噬细胞中的抗炎作用。我们证明，化合物 1 和 2 通过抑制诱导型一氧化氮合酶 (iNOS) 和环氧合酶-2 (COX-2) 蛋白表达，显着抑制 LPS 诱导的一氧化氮 (NO) 和前列腺素 E2 (PGE2) 产生，而不影响细胞活力。我们还证明，这些化合物可以减少促炎细胞因子的分泌，例如肿瘤坏死因子-α (TNF-α)、白介素-1β (IL-1β) 和白细胞介素-6 (IL-6)。此外，化合物1和2通过抑制IκB (IκB)的磷酸化来抑制LPS诱导的核因子-κB (NF-κB)活化。这些结果表明这些苯甲醛衍生物在LPS刺激的RAW264.7巨噬细胞中的抗炎作用是由于NF-κB通路的失活所致。此外，化合物 1 和 2 通过核转录因子-E2 相关因子 2 (Nrf2) 易位诱导血红素加氧酶-1 (HO-1) 表达。 HO-1 抑制剂锡原卟啉 (SnPP) 逆转了化合物 1 和 2 对促炎介质产生和 NF-κB 结合活性的抑制作用。因此，化合物1和2的抗炎作用也与其诱导HO-1表达的能力相关。
Two benzaldehyde derivatives, flavoglaucin (1) and isotetrahydro-auroglaucin (2), were isolated from the marine fungus Eurotium sp. SF-5989 through bioassay- and 1H NMR-guided investigation. In this study, we evaluated the anti-inflammatory effects of these compounds in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We demonstrated that compounds 1 and 2 markedly inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression without affecting cell viability. We also demonstrated that the compounds reduced the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Furthermore, compounds 1 and 2 inhibited LPS-induced nuclear factor-κB (NF-κB) activation by suppressing phosphorylation of IkappaB (IκB). These results indicated that the anti-inflammatory effects of these benzaldehyde derivatives in LPS-stimulated RAW264.7 macrophages were due to the inactivation of the NF-κB pathway. In addition, compounds 1 and 2 induced heme oxygenase-1 (HO-1) expression through the nuclear transcription factor-E2–related factor 2 (Nrf2) translocation. The inhibitory effects of compounds 1 and 2 on the production of pro-inflammatory mediators and on NF-κB binding activity were reversed by HO-1 inhibitor tin protoporphyrin (SnPP). Thus, the anti-inflammatory effects of compounds 1 and 2 also correlated with their ability of inducing HO-1 expression.
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影响因子：
5.1
作者：
Gao J;León F;Radwan MM;Dale OR;Husni AS;Manly SP;Lupien S;Wang X;Hill RA;Dugan FM;Cutler HG;Cutler SJ
通讯作者：
Cutler SJ
影响因子：
4.2
作者：
Berenbaum, F
通讯作者：
Berenbaum, F
影响因子：
4.8
作者：
Lee, TS;Tsai, HL;Chau, LY
通讯作者：
Chau, LY
影响因子：
10.5
作者：
Itoh, K;Wakabayashi, N;Yamamoto, M
通讯作者：
Yamamoto, M
影响因子：
3.5
作者：
Lee, Dong-Sung;Jeong, Gil-Saeng;Kim, Youn-Chul
通讯作者：
Kim, Youn-Chul