Ege University Central Research Testing and Analysis Laboratory Research and Application Center, 35100, Bornova, Izmir, Turkey.
Ege University, Faculty of Science, Department of Physics, 35100, Bornova, Izmir, Turkey.
Chem Biol Interact. 2022 Oct 1;366:110131. doi: 10.1016/j.cbi.2022.110131. Epub 2022 Aug 28.
Since cell membranes are complex systems, the use of model lipid bilayers is quite important for the study of their interactions with bioactive molecules. Mammalian cell membranes require cholesterol (CHOL) for their structure and function. For this reason, the mixtures of phospholipid and cholesterol are necessary to use in model membrane studies to better simulate the real systems. In the present study, we investigated the effect of the incorporation of hesperidin in model membranes consisting of dimyristoylphosphatidylcholine (DMPC) and CHOL by using differential scanning calorimetry (DSC), attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, and atomic force microscopy (AFM). ATR-FTIR results demonstrated that hesperidin increases the fluidity of the DMPC/CHOL binary system. DSC findings indicated that the presence of 5 mol% hesperidin induces a broadening of the main phase transition consisting of three overlapping components. AFM experiments showed that hesperidin increases the thickness of DMPC/CHOL lipid bilayer model membranes. In addition to experimental results, molecular docking studies were conducted with hesperidin and human lanosterol synthase (LS), which is an enzyme found in the final step of cholesterol synthesis, to characterize hesperidin's interactions with its surrounding via its hydroxyl and oxygen groups. Then, hesperidin's ADME/Tox (absorption, distribution, metabolism, excretion and toxicity) profile was computed to see the potential impact on living system. In conclusion, considering the data obtained from experimental studies, this work ensures molecular insights in the interaction between a flavonoid, as an antioxidant drug model, and lipids mimicking those found in mammalian membranes. Moreover, computational studies demonstrated that hesperidin may be a great potential for use as a therapeutic agent for hypercholesterolemia due to its antioxidant property.
由于细胞膜是复杂的系统，因此使用模型脂质双层对于研究它们与生物活性分子的相互作用非常重要。哺乳动物细胞膜的结构和功能需要胆固醇（CHOL）。出于这个原因，在模型膜研究中需要使用磷脂和胆固醇的混合物，以更好地模拟真实系统。在本研究中，我们通过差示扫描量热法（DSC）、衰减全反射傅里叶变换红外（ATR-FTIR）光谱和原子力显微镜（AFM）研究了橙皮苷在由二肉豆蔻酰基磷脂酰胆碱（DMPC）和 CHOL 组成的模型膜中的作用。ATR-FTIR 结果表明橙皮苷增加了 DMPC/CHOL 二元体系的流动性。DSC 结果表明，存在 5 mol%的橙皮苷会引起主相变的展宽，该相变由三个重叠的成分组成。AFM 实验表明橙皮苷增加了 DMPC/CHOL 脂质双层模型膜的厚度。除了实验结果外，还对橙皮苷和人类羊毛甾醇合酶（LS）进行了分子对接研究，LS 是胆固醇合成最后一步中发现的一种酶，以通过其羟基和氧基团来表征橙皮苷与其周围环境的相互作用。然后，计算了橙皮苷的 ADME/Tox（吸收、分布、代谢、排泄和毒性）特征，以了解其对活系统的潜在影响。总之，考虑到实验研究获得的数据，这项工作确保了在抗氧化药物模型黄酮类化合物与模拟哺乳动物膜中脂质之间的相互作用方面的分子见解。此外，计算研究表明，由于其抗氧化特性，橙皮苷可能是治疗高胆固醇血症的潜在药物。
