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西红花酸对糖化人低密度脂蛋白的作用:一种保护和机制方法。

Effect of crocin on glycated human low-density lipoprotein: A protective and mechanistic approach.

机构信息

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.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2023 Feb 5;286:121958. doi: 10.1016/j.saa.2022.121958. Epub 2022 Oct 10.

DOI:10.1016/j.saa.2022.121958
PMID:36244155
Abstract

Human low-density lipoprotein (LDL) is known to have a role in coronary artery diseases when it undergoes modification due to hyperglycaemic conditions. Plant products like crocin play an essential role in protecting against oxidative stress and in the production of advanced glycation end-products (A.G.E.s). In this study, the anti-glycating effect of crocin was analyzed using various biochemical, spectroscopic, and in silico approaches. Glycation-mediated oxidative stress was confirmed by nitroblue tetrazolium, carbonyl content, and lipid peroxidation assays, and it was efficiently protected by crocin in a concentration-dependent manner. A.N.S. fluorescence, thioflavin T (ThT) assay, and electron microscopy confirmed that the structural changes in LDL during glycation lead to the formation of fibrillar aggregates, which can be minimized by crocin treatment. Moreover, secondary structural perturbations in LDL were observed using circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR), where crocin was found to prevent the loss of secondary structure in glycated LDL. Spectroscopic studies like U.V. absorbance, fluorescence spectroscopy, CD, FTIR, and fluorescence resonance energy transfer (FRET) provided insights into the interaction mechanism between LDL and crocin. Molecular docking supports these results with a highly negative binding energy of -10.3 kcal/mol, suggesting the formation of a stable ldl-crocin complex. Our study indicates that crocin may be a potent protective agent against coronary artery diseases by limiting the glycation of LDL in people with such disorders.

摘要

人低密度脂蛋白(LDL)在高血糖条件下发生修饰时,已知在冠状动脉疾病中起作用。植物产物如藏红花素在防止氧化应激和产生晚期糖基化终产物(A.G.E.)方面发挥着重要作用。在这项研究中,使用各种生化、光谱和计算方法分析了藏红花素的抗糖化作用。硝基四唑蓝、羰基含量和脂质过氧化测定证实了糖化介导的氧化应激,藏红花素以浓度依赖的方式有效地保护了这种应激。A.N.S.荧光、硫代黄素 T(ThT)测定和电子显微镜证实,LDL 在糖化过程中的结构变化导致纤维状聚集的形成,而藏红花素处理可以最小化这种聚集。此外,使用圆二色性(CD)和傅里叶变换红外光谱(FTIR)观察到 LDL 的二级结构扰动,发现藏红花素可以防止糖化 LDL 中二级结构的丢失。光谱研究如紫外吸收、荧光光谱、CD、FTIR 和荧光共振能量转移(FRET)提供了 LDL 与藏红花素之间相互作用机制的见解。分子对接支持这些结果,其结合能为-10.3 kcal/mol,表明形成了稳定的 LDL-藏红花素复合物。我们的研究表明,藏红花素可能是一种有效的保护剂,可以限制患有此类疾病的人的 LDL 糖化,从而预防冠状动脉疾病。

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