Effects of unsaturated fatty acids on the interaction between phloretin and xanthine oxidase: Inhibitory activity, binding ability and molecular structure

Inhibition of xanthine oxidase (XO) activity is an effective strategy for the treatment of hyperuricemia and gout. However, some nutrients (such as lipids, proteins, and vitamins, etc) in the daily diet may affect the binding of enzyme inhibitors to XO. The effects of three unsaturated fatty acids (USFAs, namely oleic acid, linoleic acid and α-linolenic acid) on the inhibition of XO by phloretin were investigated in the study. The results showed that USFAs significantly enhanced the inhibitory effect of phloretin on XO, primarily due to the changes in secondary structure and increased binding affinity. The order of enhancement was α-linolenic acid > oleic acid > linoleic acid. The USFAs synergistically destroyed the hydrogen bond network structure of XO with phloretin, resulting in a looser and more disordered XO structure. Moreover, phloretin formed more hydrogen bonds, hydrophobic interactions and van der Waals forces with the amino acid residues of XO in the presence of USFAs, which eventually increased the inhibitory ability of phloretin on XO. The study may provide a new perspective for the dietary nutrition intervention of the patients with hyperuricemia and gout.