Glycation is the result of covalent bonding of a free amino group of biological macromolecules with a reducing sugar, which results in the formation of a Schiff base that undergoes rearrangement, dehydration and cyclization to form a more stable Amadori product. The final products of nonenzymatic glycation of biomacromolecules like DNA, proteins and lipids are known as advanced glycation end products (AGEs). AGEs may be generated rapidly or over long times stimulated by distinct triggering mechanisms, thereby accounting for their roles in multiple settings and disease states. Both Schiff base and Amadori glycation products generate free radicals resulting in decline of antioxidant defense mechanisms and can damage cellular organelles and enzymes. This critical review primarily focuses on the mechanistic insight of glycation and the most probable route for the formation of glycation products and their therapeutic interventions. Furthermore, the prevention of glycation reaction using therapeutic drugs such as metformin, pyridoxamine and aminoguanidine (AG) are discussed with special emphasis on the novel concept of the bioconjugation of these drugs like, AG with gold nanoparticles (GNPs). At or above 10 mM concentration, AG is found to be toxic and therefore has serious health concerns, and the study warrants doing this novel bioconjugation of AG with GNPs. This approach might increase the efficacy of the AG at a reduced concentration with low or no toxicity. Using the concept of synthesis of GNPs with abovementioned drugs, it is assumed that toxicity of various drugs which are used at high doses can be minimized more effectively.

The present study onPhyllanthus virgatus, known traditionally for its remedial potential, for the first time provides descriptions of the antioxidant and inhibition ofα-amylase enzyme activity first byin vitroanalyses, followed by a confirmatoryin silicostudy to create a stronger biochemical rationale. Our results illustrated thatP. virgatusmethanol extract exhibited strong antioxidant and oxidative DNA damage protective activity than other extracts, which was well correlated with its total phenolic content. In addition,P. virgatusmethanol extract strongly inhibited theα-amylase activity (IC₅₀33.20 ± 0.556 μg/mL), in a noncompetitive manner, than acarbose (IC₅₀76.88 ± 0.277 μg/mL), which showed competitive inhibition. Moreover, this extract stimulated the glucose uptake activity in 3T3-L1 cells and also showed a good correlation between antioxidant andα-amylase activities. The molecular docking studies of the major bioactive compounds (9,12-octadecadienoic acid, asarone, 11-octadecenoic acid, and acrylic acid) revealed via GC-MS analysis from this extract mechanistically suggested that the inhibitory property may be due to the synergistic effect of these bioactive compounds. These results provide substantial basis for the future use ofP. virgatusmethanol extract and its bioactive compound inin vivosystem for the treatment and management of diabetes as well as in the related condition of oxidative stress.