# Phloroglucinol inhibited glycation via entrapping carbonyl intermediates

## TL;DR

Phloroglucinol, an antispasmodic drug, was found to inhibit glycation by trapping carbonyl intermediates, suggesting it could be repurposed as an anti-glycation agent.

## Contribution

This study demonstrates that Phloroglucinol inhibits glycation through carbonyl entrapment, not lysine blockade, offering a novel repurposing strategy.

## Key findings

- Phloroglucinol significantly reduced AGE formation with an IC50 of 0.3mM.
- BSA conformation was preserved, and fructosamine adducts and free lysine load were reduced.
- Mechanistic data showed carbonyl entrapment, not lysine blockade, was responsible for anti-glycation effects.

## Abstract

Advanced glycation end products (AGEs) play an important role in the pathogenesis of age-linked disorders and diabetes mellitus. The aim of this study was to assess the repurposing potential of Phloroglucinol (PHL the antispasmodic drug), as an anti-glycation agent using Fructose-BSA model. The ability of PHL to inhibit AGE formation was evaluated using AGEs formation (Intrinsic fluorescence), fructosamine adduct (NBT) and free lysine availability (TNBSA) assays. The BSA protein conformation was assessed through Thioflavin-T, Congo-Red and Circular Dichroism assays. The lysine blockade and carbonyl entrapment were explored as possible mode of action. Our data showed that PHL significantly decreased the formation of AGEs with an IC50 value of 0.3mM. The fructosamine adducts and free lysine load was found to be reduced. Additionally, the BSA conformation was preserved by PHL. Mechanistic assays did not reveal involvement of lysine blockade as underlying reason for reduction in AGEs load. This was also supported by computational data whereby PHL failed to engage any catalytic residue involved in early fructose-BSA interaction. However, it was found to entrap the carbonyl moieties. In conclusion, the PHL demonstrated anti-glycation potential, which can be attributed to its ability to entrap carbonyl intermediates. Hence, the clinically available antispasmodic drug, presents itself as a promising candidate to be repurposed as anti-glycation agent.