Meloxicam Inhibited the Glycation Phenomenon via Scavenging Di-Carbonyl Moieties
TL;DR
It is demonstrated that MEL possess anti-glycation potential, which can be attributed to entrapment of carbonyl intermediates, which presents itself as promising candidate to be repurposed against deleterious phenomenon of glycation.
Abstract
Senescence or aging is often associated with onset of morbidities, which have been attributed to the harmful phenomenon of glycation. To date, no drug is available to combat this deleterious process. The drug repurposing is a robust and cost-effective approach to identify potential candidate molecules for drug discovery programs. In present study, Meloxicam (MEL) was evaluated for its capacity to be repurposed against glycation. Using the Fructose-BSA model, the anti-glycation effect was evaluated by measuring intrinsic fluorescence of Advanced Glycation End Products (AGEs). The fructoseamine load and free lysine availability was estimated using NBT and TNBSA assays respectively. The BSA secondary structure was assessed by Thioflavin-T, Congo red and Circular Dichroism tests. Finally, lysine blockade and carbonyl entrapment was evaluated as a possible mode of anti-glycation action. Our data showed that MEL (0.5, 1, and 2mM) has significantly reduced the AGEs formation (IC50 = 0.25mM). The load of fructosamine adducts along with free lysine availability was found to be reduced. The secondary structure of BSA was preserved. Regarding mode of action, MEL did not block lysine residues, which was also supported by computational data. However, it was found to entrap carbonyl intermediates. In conclusion, the present study demonstrate that MEL possess anti-glycation potential, which can be attributed to entrapment of carbonyl intermediates. Hence, MEL, a clinically used NSAIDs, present itself as promising candidate to be repurposed against deleterious phenomenon of glycation.