Anti-inflammatory effect of Apo-9′-fucoxanthinone via inhibition of MAPKs and NF-kB signaling pathway in LPS-stimulated RAW 264.7 macrophages and zebrafish model
Anti-inflammatory effect of Apo-9′-fucoxanthinone via inhibition of MAPKs and NF-kB signaling pathway in LPS-stimulated RAW 264.7 macrophages and zebrafish model
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DOI：
10.1016/j.intimp.2018.03.034
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发表时间：
2018-06-01
影响因子：
5.6
通讯作者：
Heo, Soo-Jin
中科院分区：
文献类型：
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作者：
Kim, Eun-A;Kim, Seo-Young;Heo, Soo-Jin
在这项研究中，我们在体外RAW 264.7细胞和体内斑马鱼模型中证实了Apo-9-岩藻黄酮（AF）的抗炎作用。在脂多糖（LPS）刺激的斑马鱼，AF显着降低活性氧（ROS），一氧化氮（NO）的产生和细胞死亡。诱导型一氧化氮合酶（iNOS）、抑制型环氧合酶-2（考克斯-2）和炎性细胞因子IL-1 β、TNF-α的mRNA表达降低。AF能显著抑制LPS刺激的RAW 264.7细胞NO的产生和iNOS的表达。此外，AF在25、50和100 μ g/mL时分别抑制考克斯-2、前列腺素E2（PGE 2）和促炎细胞因子，如白细胞介素-6（IL-6）、IL-1 β和肿瘤坏死因子-α（TNF-α）。进一步的机制研究表明，AF抑制核因子-kB（NF-kB）通路和丝裂原活化蛋白激酶（MAPK）通路分子如细胞外信号调节激酶（ERK）和c-Jun N-末端激酶（JNK）的磷酸化。根据上述结果，AF可以作为一种有用的抗炎剂在营养品或药物中使用。
In this study, we confirmed the anti-inflammatory effect of Apo-9-fucoxanthinone (AF) in in vitro RAW 264.7 cells and in vivo zebrafish model. In lipopolysaccharide (LPS)-stimulated zebrafish, AF significantly decreased the production of reactive oxygen species (ROS), nitric oxide (NO) and cell death. In addition, the mRNA expression of inducible nitric oxide synthase (iNOS), suppressed cyclooxygenase-2 (COX-2) and an inflammatory cytokines; IL-1 beta, TNF-alpha were shown reduction. And AF significantly inhibited NO production and expression of iNOS in LPS-stimulated RAW 264.7 cells. Further, AF suppressed COX-2, prostaglandin E2 (PGE2), and pro-inflammatory cytokines such as interleukin-6 (IL-6), IL-1 beta and tumor necrosis factor-alpha (TNF-alpha) at 25, 50 and 100 mu g/mL, respectively. Further mechanistic studies showed that AF suppressed the nuclear factor-kB (NF-kB) pathway and phosphorylation of mitogen-activated protein kinase (MAPK) pathway molecules such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). According to the results, AF can be used and applied as a useful anti-inflammatory agent of nutraceutical or pharmaceutical.