In vitro and in silico studies and a systematic literature review of antiglycation properties of amlodipine.

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.