Abstract
The development of advanced glycation end-products (AGEs) inhibitors is considered to have therapeutic potential in diabetic complications inhibiting the loss of the biomolecular function. In the present study, zinc oxide nanoparticles (ZnO-NPs) were synthesized from aqueous leaf extract of Morus indica and were characterized by various techniques such as ultraviolet (UV)-Vis spectroscopy, Powder X-Ray Diffraction (PXRD), Fourier Transform Infrared Spectroscopy (FT-IR), Scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). Further, the inhibition of AGEs formation after exposure to ZnO-NPs was investigated by in-vitro, in-vivo, and molecular docking studies. Biochemical and histopathological changes after exposure to ZnO-NPs were also studied in streptozotocin-induced diabetic rats. ZnO-NPs showed an absorption peak at 359 nm with a purity of 92.62% and ~6–12 nm in size, which is characteristic of nanoparticles. The images of SEM showed agglomeration of smaller ZnO-NPs and EDS authenticating that the synthesized nanoparticles were without impurities. The biosynthesized ZnO-NPs showed significant inhibition in the formation of AGEs. The particles were effective against methylglyoxal (MGO) mediated glycation of bovine serum albumin (BSA) by inhibiting the formation of AGEs, which was dose-dependent. Further, the presence of MGO resulted in complete damage of biconcave red blood corpuscles (RBCs) to an irregular shape, whereas the morphological changes were prevented when they were treated with ZnO-NPs leading to the prevention of complications caused due to glycation. The administration of ZnO-NPs (100 mg Kg−1) in streptozotocin(STZ)-induced diabetic rats reversed hyperglycemia and significantly improved hepatic enzymes level and renal functionality, also the histopathological studies revealed restoration of kidney and liver damage nearer to normal conditions. Molecular docking of BSA with ZnO-NPs confirms that masking of lysine and arginine residues is one of the possible mechanisms responsible for the potent antiglycation activity of ZnO-NPs. The findings strongly suggest scope for exploring the therapeutic potential of diabetes-related complications.
Highlights
Advanced glycation end products (AGEs) are heterogeneous compounds that are formed when protein or lipid exposed to sugar in the bloodstream
The exact mechanism involved in the formation of zinc oxide nanoparticles (ZnO-NPs) from plant extracts has not been reported, but it has been quoted that polar groups are responsible for it [31,32,33]
M. indica was used for the first time to biosynthesize zinc oxide nanoparticles (ZnO-NPs) from the aqueous leaf extract to evaluate the potential to inhibit advanced glycation end-products (AGEs) formation
Summary
Advanced glycation end products (AGEs) are heterogeneous compounds that are formed when protein or lipid exposed to sugar in the bloodstream. AGEs are produced by a sequence of events (Maillard reaction), wherein the sugars react with free amino groups of peptides, proteins, and amino acids with lysine and arginine residues to form a ketoamine known as Amadori product, which is associated with the diabetic complications[1,2,3,4,5]. Advanced glycation endproducts lead to chemical modifications in the targeted protein which, in turn, undergoes specific changes such as detachment of ligands and oxidation of thiol group leading to the formation of disulfide linkage or thiol radicals [6]. AGEs inhibitors such as pyridoxamine [9], tenilsetam [10], and metformin [11]
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