Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387, Kraków, Poland.
Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland, Gronostajowa 7A, 30-387, Kraków, Poland.
Cell Biochem Biophys. 2020 Jun;78(2):139-147. doi: 10.1007/s12013-020-00906-5. Epub 2020 Apr 1.
Curcumin is a yellow-orange dye widely used as a spice, food coloring and food preservative. It also exhibits a broad range of therapeutic effects against different disorders such as cancer, diabetes, or neurodegenerative diseases. As a compound insoluble in water curcumin accumulates in cell membranes and due to this location it may indirectly lead to the observed effects by structurally altering the membrane environment. To exert strong structural effects on membrane curcumin needs to adopt a transbilayer orientation. However, there is no agreement in literature as to curcumin's orientation and its structural effects on membranes. Here, we investigated the effects of curcumin on lipid order, lipid phase transition, and local polarity in a model liposome membranes made of DMPC or DSPC using electron paramagnetic resonance (EPR) spin labeling technique. Curcumin affected lipid order at different depths within the membrane: it slightly increased the phospholipid polar headgroup mobility as monitored by spectral parameters of T-PC, while along the acyl chain the ordering effect was observed in terms of order parameter S. Also, rotational correlation times τ and τ of 16-PC in the membrane center were increased by curcumin. Polarity measurements performed in frozen suspensions of liposomes revealed enhancement of water penetration by curcumin in the membrane center (16-PC) and in the polar headgroup region (T-PC) while the intermediate positions along the acyl chain (5-PC and 10-PC) were not significantly affected. Curcumin at a lower concentration (5 mol%) shifted the temperature of the DMPC main phase transition to lower values and increased the transition width, and at a higher concentration (10 mol%) abolished the transition completely. The observed effects suggest that curcumin adopts a transbilayer orientation within the membrane and most probably form oligomers of two molecules, each of them spanning the opposite bilayer leaflets. The effects are also discussed in terms of curcumin's protective activity and compared with those imposed on membranes by other natural dyes known for their protective role, namely polar carotenoids, lutein and zeaxanthin.
姜黄素是一种广泛用作香料、食用色素和食品防腐剂的黄橙色染料。它还表现出对各种疾病的广泛治疗效果，如癌症、糖尿病或神经退行性疾病。由于姜黄素是一种不溶于水的化合物，它会在细胞膜中积累，由于这种位置，它可能会通过改变膜环境的结构，间接地导致观察到的效果。为了对膜产生强烈的结构影响，姜黄素需要采用跨双层取向。然而，关于姜黄素的取向及其对膜的结构影响，文献中没有达成一致意见。在这里，我们使用电子顺磁共振（EPR）自旋标记技术研究了姜黄素对由 DMPC 或 DSPC 制成的模型脂质体膜中脂质有序性、脂质相变和局部极性的影响。姜黄素在膜内的不同深度影响脂质有序性：它略微增加了磷脂极性头部基团的流动性，如 T-PC 的光谱参数所监测的那样，而在酰基链上，则观察到有序参数 S 的有序效应。此外，膜中心的 16-PC 的旋转相关时间 τ 和 τ 也被姜黄素增加。在脂质体的冷冻悬浮液中进行的极性测量表明，姜黄素增强了膜中心（16-PC）和极性头部基团区域（T-PC）的水渗透，而在酰基链的中间位置（5-PC 和 10-PC）则没有明显影响。在较低浓度（5 mol%）下，姜黄素将 DMPC 主相变的温度降低到更低的值，并增加了相变宽度，而在较高浓度（10 mol%）下，完全消除了相变。观察到的效应表明，姜黄素在膜内采用跨双层取向，并且很可能形成两个分子的寡聚物，每个分子跨越相反的双层叶。还讨论了这些效应，以及它们与其他天然染料对膜的影响进行比较，这些天然染料以其保护作用而闻名，即极性类胡萝卜素、叶黄素和玉米黄质。
