Department of Biochemistry, J.N.M.C., Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, U.P., India.
Department of Biochemistry, J.N.M.C., Faculty of Medicine, Aligarh Muslim University, Aligarh 202002, U.P., India.
Int J Biol Macromol. 2023 May 31;238:124151. doi: 10.1016/j.ijbiomac.2023.124151. Epub 2023 Mar 22.
Glycation of human low-density protein (LDL) has an essential contribution to cardiovascular diseases. Natural compounds like rutin have been extensively studied in preventing glycation-induced oxidative stress. This study examined rutin's anti-glycation potential with glycated LDL utilizing spectroscopic and in silico methods. Glycated LDL treated with rutin, showed around 80 % inhibition in advanced glycation end-product production. Carbonyl content and lipid peroxidation like assays were used to establish the development of oxidative stress. Rutin was seen to lower the generation of oxidative stress in a dose-dependent manner. Using thioflavin-T assay and electron microscopy, rutin was suggested to restore the structural disturbances in glycated LDL. Moreover, CD spectroscopy suggested reinstation of secondary structure of glycated LDL treated with rutin. Mechanistic insights between rutin and LDL were observed through spectroscopic measures. Molecular docking study confirmed the LDL-rutin binding with a binding energy of -10.0 kcal/mol. The rutin-LDL complex was revealed to be highly stable by molecular dynamics simulation, with RMSD, RMSF, Rg, SASA, and the secondary structure of LDL remaining essentially unchanged during the simulation period. Our study suggests that rutin possesses strong anti-glycating properties, which can be useful in therapeutics, as glycated LDL has an important role in atherosclerotic cardiovascular diseases.
人低密度脂蛋白（LDL）的糖化对心血管疾病有重要贡献。芦丁等天然化合物已被广泛研究用于预防糖基化诱导的氧化应激。本研究利用光谱和计算方法研究了芦丁对糖化 LDL 的抗糖化潜力。用芦丁处理的糖化 LDL，其晚期糖基化终产物的产生抑制率约为 80%。羰基含量和脂质过氧化测定等方法用于建立氧化应激的发展。芦丁被发现以剂量依赖的方式降低氧化应激的产生。通过硫代黄素-T 测定和电子显微镜观察，芦丁被认为可以恢复糖化 LDL 的结构紊乱。此外，CD 光谱表明，芦丁可以恢复糖化 LDL 的二级结构。通过光谱测量观察到芦丁与 LDL 之间的相互作用机制。分子对接研究证实了 LDL-芦丁的结合，结合能为-10.0 kcal/mol。通过分子动力学模拟证实了芦丁-LDL 复合物具有高度稳定性，在模拟期间，LDL 的 RMSD、RMSF、Rg、SASA 和二级结构基本保持不变。我们的研究表明，芦丁具有很强的抗糖化特性，这在治疗中可能很有用，因为糖化 LDL 在动脉粥样硬化性心血管疾病中起重要作用。
