Chang Chi-Fen, Liao Kang-Chun, Chen Chung-Hwan
Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan.
Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan.
PLoS One. 2017 Jan 6;12(1):e0168945. doi: 10.1371/journal.pone.0168945. eCollection 2017.
The anti-inflammatory pharmacological effect of eight 2-phenylnaphthalenes (PNAP-1-PNAP-8) on lipopolysaccharide (LPS)-induced RAW 264.7 (a mouse cell line) was investigated. Among them, 6,7-dihydroxy-2-(4'-hydroxyphenyl)naphthalene (PNAP-6) and 2-(4'-aminophenyl)-6,7-dimethoxynaphthalene (PNAP-8) exhibited the best anti-inflammatory activity in this study. PNAP-6 and PNAP-8 not only significantly decreased the expression of inducible nitric oxide synthase and cyclooxygenase-II, but also inhibited the production of nitric oxide, interleukin-6, and tumor necrosis factor-α in LPS stimulated cells. Moreover, PNAP-6 and PNAP-8 inhibited nuclear factor (NF)-κB activation by decreasing the degradation of IκB and nuclear translocation of NF-κB subunit (p65). In addition, PNAP-6 and PNAP-8 also attenuated the phosphorylation of ERK, p38, and JNK. These results suggest that PNAP-6 and PNAP-8 exert anti-inflammatory activities by down regulating NF-κB activation and the mitogen-activated protein kinase signaling pathway in LPS-stimulated Raw 264.7 cells. This is the first study demonstrating that PNAPs can inhibit LPS-induced pro-inflammatory mediators in macrophages cells.
研究了8种2-苯基萘（PNAP-1-PNAP-8）对脂多糖（LPS）诱导的RAW 264.7（一种小鼠细胞系）的抗炎药理作用。其中，6,7-二羟基-2-（4'-羟基苯基）萘（PNAP-6）和2-（4'-氨基苯基）-6,7-二甲氧基萘（PNAP-8）在本研究中表现出最佳的抗炎活性。PNAP-6和PNAP-8不仅显著降低诱导型一氧化氮合酶和环氧化酶-II的表达，还抑制LPS刺激细胞中一氧化氮、白细胞介素-6和肿瘤坏死因子-α的产生。此外，PNAP-6和PNAP-8通过减少IκB的降解和NF-κB亚基（p65）的核转位来抑制核因子（NF）-κB的激活。此外，PNAP-6和PNAP-8还减弱了ERK、p38和JNK的磷酸化。这些结果表明，PNAP-6和PNAP-8通过下调LPS刺激的Raw 264.7细胞中NF-κB的激活和丝裂原活化蛋白激酶信号通路发挥抗炎活性。这是第一项证明PNAPs可抑制巨噬细胞中LPS诱导的促炎介质的研究。
