REQUIMTE, Laboratório de Química Aplicada, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal.
Eur J Med Chem. 2013 Sep;67:280-92. doi: 10.1016/j.ejmech.2013.06.019. Epub 2013 Jun 21.
Inflammation is a normal response towards tissue injury, but may become deleterious to the organism if uncontrolled. The overproduction of reactive species during the inflammatory process may cause or magnify the damage at inflammatory sites. Flavonoids have been suggested as therapeutic agents to avoid such damage, as these compounds exhibit anti-inflammatory activity, through the modulation of oxidative stress and signalling pathways. Both effects may attenuate neutrophils' activities at inflammatory sites. In this study, we investigated the structure/activity relationship of a series of flavonoids on the oxidative burst of human neutrophils in vitro, as a measure of its anti-inflammatory potential. Neutrophils were stimulated with phorbol-12-myristate-13-acetate, and fluorescence and chemiluminescence techniques were used to evaluate the generation of reactive oxygen species. All the tested flavonoids revealed the ability to modulate the neutrophil's oxidative burst. From the obtained results, the pivotal role of the catechol group in the B-ring was evidenced as well as the minor importance of the hydroxylations in the A-ring, which did not appear to be determinant for the activity, although clearly influencing the lipophilicity of the tested flavonoids. It is also clarified the importance of the methylation in the OH group at the B-ring catechol moiety. In conclusion, the obtained results uncover new possible strategies for the resolution of inflammatory processes, using flavonoids to modulate neutrophil's oxidative burst.
炎症是组织损伤的正常反应，但如果不受控制，可能会对机体造成损害。在炎症过程中，活性物质的过度产生可能会导致或加剧炎症部位的损伤。黄酮类化合物被认为是一种治疗剂，可以避免这种损伤，因为这些化合物通过调节氧化应激和信号通路表现出抗炎活性。这两种作用都可以减弱中性粒细胞在炎症部位的活性。在这项研究中，我们研究了一系列黄酮类化合物对人中性粒细胞体外氧化爆发的结构-活性关系，作为其抗炎潜力的衡量标准。用佛波醇 12-肉豆蔻酸 13-乙酸酯刺激中性粒细胞，并使用荧光和化学发光技术评估活性氧的产生。所有测试的黄酮类化合物都显示出调节中性粒细胞氧化爆发的能力。从获得的结果中，证据表明 B 环中的儿茶酚基团起着关键作用，而 A 环中的羟基化作用的重要性较小，这似乎不是决定活性的因素，尽管明显影响了测试的黄酮类化合物的亲脂性。还阐明了 B 环儿茶酚部分 OH 基团甲基化的重要性。总之，获得的结果揭示了使用黄酮类化合物调节中性粒细胞氧化爆发来解决炎症过程的新策略。
