Ribose Mediated Glycation of Human Serum Albumin and Their Inhibition by Silibinin and 2-Hydroxy-1,4-Naphthoquinone: In Vitro and Computational Studies.

Under hyperglycemic conditions, proteins undergo structural modifications non-enzymatically, resulting in the formation of advanced glycation end products (AGEs). These AGEs contribute to the production of free radicals, which in turn exacerbate the development of diabetes and its complications. Therefore, inhibiting glycation is anticipated to play a crucial role in managing diabetes. Here, we have examined the effect of 2-hydroxy-1,4-naphthoquinone (NQ) and silibinin on ribose-mediated glycation of HSA. Presence of NQ and silibinin inhibited the fluorescent AGEs formation by 79.18% and 84.10%, respectively. Moreover, the secondary structural loss caused by glycation was restored by NQ and silibinin treatment. Both the compounds showed higher affinity toward native HSA compared to glycated HSA as evident from their binding constants. Molecular docking showed a direct interaction of tested compounds with glycation prone amino acids arginine and lysine residues of HSA. Molecular simulation studies confirmed the NQ or silibinin formed stable complex with HSA. Both the ligands formed hydrogen bonds throughout the trajectory. MM-PBSA calculation showed the overall binding energies for silibinin and NQ with HSA were −16.863 kcal/mol and −9.977 kcal/mol, respectively. The findings show the antiglycation potential of NQ and silibinin against ribose mediated glycation of HSA along with mode of action. Advanced glycation end products (AGEs) contribute to the development of diabetes and its complications. 2-hydroxy-1,4-naphthoquinone (NQ) and silibinin inhibited the fluorescent AGEs formation by 79.18% and 84.10%, respectively. Molecular docking showed a direct interaction of NQ and silibinin with lysine and arginine residues of HSA [ABSTRACT FROM AUTHOR]