Department of Pharmacology, College of Medicine, University of Hail, Hail, Saudi Arabia.
Department of Pathology, College of Medicine, University of Hail, Hail, Saudi Arabia.
Cell Biochem Funct. 2022 Oct;40(7):729-741. doi: 10.1002/cbf.3738. Epub 2022 Sep 13.
The generation of advanced glycation end products (AGEs) through nonenzymatic protein glycation contributes to the pathogenesis of long-lived diabetic problems. Metformin (MTF) is the very first drug having antihyperglycemic effects on type II diabetes mellitus which also possess interaction with dicarbonyl compounds and blocks the formation of AGEs. In the current study, MTF is bioconjugated with glycation-derived synthesized gold nanoparticles (GNPs) of significant size. Additionally, using various biophysical and biochemical approaches, we investigated the antiglycating capacity MTF-GNPs in contrast to MTF against d-ribose-derived glycation of bovine serum albumin. Our key findings via utilizing various assays demonstrated that MTF-GNPs were able to inhibit AGEs development by reducing hyperchromicity, early glycation products, carbonyl content, hydxoxymethylfurfural content, production of fluorescent AGEs, normalizing the loss of secondary structure (i.e., α-helix and β-sheets) of proteins, elevating the levels of free lysine and free arginine more efficiently compared to pure MTF. Based on these results, we concluded that MTF-GNPs possess a considerable antiglycation property and may be developed as an outstanding anti-AGEs treatment drug. Further in vivo and clinical research are necessary to determine the therapeutic effects of MTF-GNPs against AGE-related and metabolic disorders.
通过非酶蛋白糖化作用生成的晚期糖基化终产物（AGEs）是导致长期糖尿病问题的发病机制之一。二甲双胍（MTF）是治疗 2 型糖尿病的第一种具有降血糖作用的药物，它还与二羰基化合物相互作用，阻止 AGEs 的形成。在目前的研究中，MTF 与糖化衍生合成的金纳米颗粒（GNPs）进行生物缀合，这些 GNPs 的尺寸非常重要。此外，我们还利用各种生物物理和生化方法，研究了 MTF-GNPs 与 MTF 相比在抗牛血清白蛋白的 d-核糖衍生糖基化方面的抗糖化能力。通过利用各种测定方法，我们的主要发现表明，MTF-GNPs 能够通过减少增色、早期糖化产物、羰基含量、羟甲基糠醛含量、荧光 AGEs 的产生、使蛋白质的二级结构（即α-螺旋和β-折叠）正常化，从而抑制 AGEs 的发展，有效地提高游离赖氨酸和游离精氨酸的水平，这比纯 MTF 更有效。基于这些结果，我们得出结论，MTF-GNPs 具有相当的抗糖化特性，可能被开发为一种出色的抗 AGEs 治疗药物。需要进一步的体内和临床研究来确定 MTF-GNPs 对与 AGE 相关的代谢紊乱的治疗效果。
