Dańkowska Karolina, Nesterowicz Miłosz, Lauko Kamil Klaudiusz, Trocka Daria, Żendzian-Piotrowska Małgorzata, Ładny Jerzy Robert, Zalewska Anna, Żebrowska-Gamdzyk Marta, Maciejczyk Mateusz
Students' Scientific Club "Biochemistry of Civilization Diseases Department of Hygiene, Epidemiology and Ergonomics , Medical University of Bialystok , 2c Mickiewicza Street, 15-233, Białystok, Poland.
Department of Hygiene, Epidemiology and Ergonomics , Medical University of Bialystok , Białystok, 2c Mickiewicza Street, 15-233, Poland.
Sci Rep. 2025 Sep 26;15(1):33277. doi: 10.1038/s41598-025-18925-8.
Protein glycation is crucial in the pathogenesis of diabetes and its cardiovascular complications. Little is known about the antiglycation properties of amlodipine, a long-acting calcium channel blocker used to treat high blood pressure. In our study, amlodipine's antiglycoxidant activity was assayed in sugars (glucose, fructose, and ribose), aldehydes (glyoxal), and chloramine T-modified bovine serum albumin (BSA). Aminoguanidine and N-acetylcysteine were used as standard glycation/oxidation inhibitors. The content of oxidation, glycoxidation, and glycation protein products was measured colorimetrically and fluorimetrically. A one-way analysis of variance (ANOVA) followed by Tukey's post hoc test was used for statistical analysis. The mechanism of amlodipine's antiglycoxidant activity was also evaluated using in-silico molecular docking. Amlodipine protects against BSA oxidation, as evidenced by enhanced total thiol content and mitigated protein carbonyls/advanced oxidation protein products. Amlodipine also increased the fluorescence of tryptophan and decreased the contents of kynurenine, N-formylkynurenine, and dityrosine. In addition, amlodipine effectively prevents protein glycation, as evidenced by a reduction in amyloid-beta structure, Amadori products, and advanced glycation end products (AGEs). In in silico analysis, amlodipine's antiglycation properties were indicated during its interaction with BSA, glycosidases, and AGEs/receptor for AGEs (RAGE) pathway proteins. Among all proteins, amlodipine docked best with c-Jun N-terminal kinases. Summarizing, we have demonstrated the anti-glycation and antioxidant activity of amlodipine in vitro. This effect may be particularly important in patients with diabetes and atherosclerosis, where excessive glycation accelerates the development of vascular complications. Further studies are needed to confirm the antidiabetic activity of amlodipine in vivo.
蛋白质糖基化在糖尿病及其心血管并发症的发病机制中至关重要。氨氯地平是一种用于治疗高血压的长效钙通道阻滞剂，其抗糖基化特性鲜为人知。在我们的研究中，在糖类（葡萄糖、果糖和核糖）、醛类（乙二醛）以及氯胺T修饰的牛血清白蛋白（BSA）中检测了氨氯地平的抗氧化活性。氨基胍和N-乙酰半胱氨酸用作标准糖基化/氧化抑制剂。通过比色法和荧光法测量氧化、糖氧化和糖基化蛋白质产物的含量。采用单因素方差分析（ANOVA），随后进行Tukey事后检验进行统计分析。还使用计算机模拟分子对接评估了氨氯地平抗氧化活性的机制。氨氯地平可防止BSA氧化，总巯基含量增加以及蛋白质羰基/晚期氧化蛋白产物减少证明了这一点。氨氯地平还增加了色氨酸的荧光，并降低了犬尿氨酸、N-甲酰犬尿氨酸和二酪氨酸的含量。此外，氨氯地平有效地防止了蛋白质糖基化，淀粉样β结构、阿马多里产物和晚期糖基化终产物（AGEs）的减少证明了这一点。在计算机模拟分析中，氨氯地平与BSA、糖苷酶以及AGEs/AGEs受体（RAGE）途径蛋白相互作用时显示出抗糖基化特性。在所有蛋白质中，氨氯地平与c-Jun氨基末端激酶的对接效果最佳。总之，我们在体外证明了氨氯地平的抗糖基化和抗氧化活性。这种作用在糖尿病和动脉粥样硬化患者中可能尤为重要，因为过度糖基化会加速血管并发症的发展。需要进一步研究以证实氨氯地平在体内的抗糖尿病活性。
