Lee Vanessa J, Heffern Marie C
Department of Chemistry, University of California, Davis, Davis, CA, United States.
Front Chem. 2022 Aug 23;10:972198. doi: 10.3389/fchem.2022.972198. eCollection 2022.
Flavonoids are polyphenolic small molecules that are abundant in plant products and are largely recognized for their beneficial health effects. Possessing both antioxidant and prooxidant properties, flavonoids have complex behavior in biological systems. The presented work investigates the intersection between the biological activity of flavonoids and their interactions with copper ions. Copper is required for the proper functioning of biological systems. As such, dysregulation of copper is associated with metabolic disease states such as diabetes and Wilson's disease. There is evidence that flavonoids bind copper ions, but the biological implications of their interactions remain unclear. Better understanding these interactions will provide insight into the mechanisms of flavonoids' biological behavior and can inform potential therapeutic targets. We employed a variety of spectroscopic techniques to study flavonoid-Cu(II) binding and radical scavenging activities. We identified structural moieties important in flavonoid-copper interactions which relate to ring substitution but not the traditional structural subclassifications. The biological effects of the investigated flavonoids specifically on copper trafficking were assessed in knockout yeast models as well as in human hepatocytes. The copper modulating abilities of strong copper-binding flavonoids were largely influenced by the relative hydrophobicities. Combined, these spectroscopic and biological data help elucidate the intricate nature of flavonoids in affecting copper transport and open avenues to inform dietary recommendations and therapeutic development.
黄酮类化合物是多酚类小分子，在植物产品中含量丰富，并因其对健康有益的作用而广为人知。黄酮类化合物兼具抗氧化和促氧化特性，在生物系统中表现出复杂的行为。本文的工作研究了黄酮类化合物的生物活性与其与铜离子相互作用之间的交叉点。铜是生物系统正常运作所必需的。因此，铜的失调与糖尿病和威尔逊氏病等代谢疾病状态有关。有证据表明黄酮类化合物能结合铜离子，但其相互作用的生物学意义仍不清楚。更好地理解这些相互作用将有助于深入了解黄酮类化合物的生物学行为机制，并为潜在的治疗靶点提供信息。我们采用了多种光谱技术来研究黄酮类化合物与铜（II）的结合以及自由基清除活性。我们确定了黄酮类化合物与铜相互作用中重要的结构部分，这些部分与环取代有关，而与传统的结构亚分类无关。在基因敲除酵母模型以及人类肝细胞中评估了所研究的黄酮类化合物对铜转运的具体生物学效应。强铜结合黄酮类化合物的铜调节能力在很大程度上受相对疏水性的影响。综合这些光谱和生物学数据，有助于阐明黄酮类化合物在影响铜转运方面的复杂性质，并为饮食建议和治疗开发提供思路。
