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The Interaction of Flavonols with Membrane Components: Potential Effect on Antioxidant Activity.
The Journal of Membrane Biology ( IF 2.4 ) Pub Date : 2020-01-02 , DOI: 10.1007/s00232-019-00105-1
Sarmistha Saha 1 , Emiliano Panieri 2 , Sibel Suzen 3 , Luciano Saso 2
Affiliation  

Abstract

Flavonols are the most widely distributed class of dietary flavonoids with a wide range of pharmacological properties due to their potent lipid peroxidation inhibition activity. The permeability and orientation of these compounds in lipid bilayers can provide an understanding of their antioxidant and lipid-peroxidation inhibition activity based on their structures at the molecular level. For this purpose, we studied antioxidant activity and atomic-scale molecular dynamics simulations of 3-hydroxyflavone (fisetin), 5-hydroxyflavone (apigenin) and 3,5-hydroxyflavone (morin) in palmitoyloleylphosphatidylcholine (POPC) membrane models with 0 mol% and 40 mol% cholesterol concentration. In pure POPC bilayer with 0 mol% cholesterol concentration, the flavonols penetrated into bilayer with lowest free energy profiles, however, incorporation of 40% cholesterol concentration reduced the permeability of the flavonols. Higher cholesterol concentrations in the POPC lipid bilayer resulted in an increase of the bilayer thickness and corresponding decrease in the area per lipid which rationalizes the reduced partitioning of flavonols due to cholesterol. In the presence of cholesterol, the flavonols reside at the polar interfacial region of the lipid bilayer to form higher H-bonding interactions with cholesterol molecules in addition to water and lipid oxygens. Among all the selected flavonols, morin showed the highest affinity which was driven by the hydrophobic effect as also depicted by ITC (Isothermal titration calorimetry) experiments and thus, more efficient antioxidant in scavenging superoxide, nitric oxide radicals as well as lipid peroxyl radicals. Furthermore, our simulations also confirmed that the permeability of compounds is sensitive towards the cholesterol content in the membrane.

Graphic Abstract



中文翻译:

黄酮醇与膜成分的相互作用:对抗氧化活性的潜在影响。

摘要

由于其有效的脂质过氧化抑制活性,黄酮醇是分布最广的一类饮食类黄酮,具有广泛的药理特性。这些化合物在脂质双层中的渗透性和方向可以基于它们在分子水平上的结构提供对它们的抗氧化剂和脂质过氧化抑制活性的了解。为此,我们在0 mol%和0 mol%的棕榈酰油基磷脂酰胆碱(POPC)膜模型中研究了3-羟基黄酮(fisetin),5-羟基黄酮(芹菜素)和3,5-羟基黄酮(morin)的抗氧化剂活性和原子级分子动力学模拟。 40 mol%胆固醇浓度。在胆固醇浓度为0 mol%的纯POPC双层中,黄酮醇以最低的自由能分布渗透到双层中,但是,40%胆固醇浓度的掺入降低了黄酮醇的渗透性。POPC脂质双层中较高的胆固醇浓度导致双层厚度增加,并且每个脂质的面积相应减少,这合理化了由于胆固醇引起的黄酮醇分配减少。在存在胆固醇的情况下,黄酮醇驻留在脂质双层的极性界面区域,除了水和脂质氧以外,还与胆固醇分子形成更高的氢键相互作用。在所有选定的黄酮醇中,香豆素显示出最高的亲和力,这是由疏水作用驱动的,ITC(等温滴定量热法)实验也表明了这一点,因此,在清除超氧化物,一氧化氮自由基和脂质过氧化自由基方面,抗氧化剂更有效。此外,

图形摘要

更新日期:2020-04-14
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