REQUIMTE/Laboratório de Farmacognosia, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
PLoS One. 2011;6(8):e24098. doi: 10.1371/journal.pone.0024098. Epub 2011 Aug 26.
The search of new anti-inflammatory drugs has been a current preoccupation, due to the need of effective drugs, with less adverse reactions than those used nowadays. Several naphthoquinones (plumbagin, naphthazarin, juglone, menadione, diosquinone and 1,4-naphthoquinone), plus p-hydroquinone and p-benzoquinone were evaluated for their ability to cause a reduction of nitric oxide (NO) production, when RAW 264.7 macrophages were stimulated with lipopolysaccharide (LPS). Dexamethasone was used as positive control. Among the tested compounds, diosquinone was the only one that caused a NO reduction with statistical importance and without cytotoxicity: an IC(25) of 1.09±0.24 µM was found, with 38.25±6.50% (p<0.001) NO reduction at 1.5 µM. In order to elucidate if this NO decrease resulted from the interference of diosquinone with cellular defence mechanisms against LPS or to its conversion into peroxynitrite, by reaction with superoxide radical formed by naphthoquinones redox cycling, 3-nitrotyrosine and superoxide determination was also performed. None of these parameters showed significant changes relative to control. Furthermore, diosquinone caused a decrease in the pro-inflammatory cytokines: tumour necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Therefore, according to the results obtained, diosquinone, studied for its anti-inflammatory potential for the first time herein, has beneficial effects in inflammation control. This study enlightens the mechanisms of action of naphthoquinones in inflammatory models, by checking for the first time the contribution of oxidative stress generated by naphthoquinones to NO reduction.
寻找新的抗炎药物一直是当前的关注点，因为需要有效的药物，其不良反应要少于目前使用的药物。几种萘醌（白花丹醌、萘醌、胡桃醌、维生素 K3、二氢萘醌和 1,4-萘醌），加上对苯二酚和对苯醌，都被评估了其抑制脂多糖（LPS）刺激 RAW 264.7 巨噬细胞产生一氧化氮（NO）的能力。地塞米松被用作阳性对照。在所测试的化合物中，只有二氢萘醌能显著降低 NO 且没有细胞毒性：在 1.5 µM 时，IC（25）为 1.09±0.24 µM，NO 降低 38.25±6.50%（p<0.001）。为了阐明这种 NO 减少是由于二氢萘醌干扰了细胞防御机制对抗 LPS，还是由于其与由萘醌氧化还原循环形成的超氧自由基反应转化为过氧亚硝酸盐，还进行了 3-硝基酪氨酸和超氧化物的测定。与对照组相比，这些参数均无显著变化。此外，二氢萘醌还降低了促炎细胞因子：肿瘤坏死因子-α（TNF-α）和白细胞介素 6（IL-6）。因此，根据所得结果，首次研究其抗炎潜力的二氢萘醌在炎症控制方面具有有益的作用。本研究通过首次检查由萘醌产生的氧化应激对 NO 减少的贡献，阐明了萘醌在炎症模型中的作用机制。
