Biosynthesized ZnO-NPs from Morus indica Attenuates Methylglyoxal-Induced Protein Glycation and RBC Damage: In-Vitro, In-Vivo and Molecular Docking Study

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.

Genotoxic and Cytotoxic Properties of Zinc Oxide Nanoparticles Phyto-Fabricated from the Obscure Morning Glory Plant Ipomoea obscura (L.) Ker Gawl

“…It may be noted through the FT-IR spectrum of ZnO-NPs that functional groups present in plant extract had complexed well to form a metal oxide as indicated by the absence of major peaks between 600 and 400 cm −1 [ 2 , 5 , 6 ]. The results affirm that during the phyto-fabrication of ZnO-NPs, the metabolites in plant extract act as capping/stabilizing agents to form a metal oxide, which is also in agreement with the conclusions of other researchers [ 6 , 9 , 25 ].…”

“…Further insight on the quantitative elemental analysis of ZnO-NPs through EDS revealed that the particles were of 88.11% purity ( Figure 4 B). Correspondingly, researchers have reported that the biosynthesis of ZnO-NPs from the extracts of plant materials exemplify better purity, which has been confirmed by XRD, SEM, and EDS analysis [ 6 , 9 , 14 , 16 ]. The FT-IR spectroscopic analysis of ZnO-NPs and aqueous plant extract helped to recognize the functional groups that were responsible for the phyto-fabrication of the nanoparticles during the reduction and stabilization.…”

“…In light of the environmental and biological risks due to the toxicity of used chemicals in synthetic metal–oxide nanoparticles, biologically synthesized nanoparticles have gained considerable importance as they are considered to be stable, eco-friendly, and also possess biological properties [ 3 , 4 , 5 , 6 ]. Different methods have been employed for the synthesis of nanoparticles, of which the hydrothermal method is one of the alternatives to the synthetic methods, as it is simple, cost-effective, eco-friendly, and less hazardous [ 7 , 8 , 9 ]. Zinc oxide nanoparticles (ZnO-NPs) have gained more attention compared to other metal–oxide nanoparticles because of their broader applications in scientific fields, including biological applications [ 8 , 10 , 11 ].…”

Carbonyl Stress in Red Blood Cells and Hemoglobin

“…Biochemical shifts in RBC are accompanied by morphological changes. Treating RBCs with MG in vitro leads to the transformation of normal biconcave cells into echinocytic ones [180]. In RBCs obtained from the blood of diabetic patients, hypochromia and anisopoikilocytosis (the spread of RBCs by size and shape) were observed [181].…”

“…We can assume that dietary polyphenols will be effective in fighting the carbonyl stress in RBCs. Zinc oxide nanoparticles (ZnO-NP) synthesized from an aqueous extract of Morus indica leaves were also reported as promising pharmacological agents with therapeutic potential at diabetic sequela [180].…”