A Study on the Interaction Between Kaempferol, Apigenin and 4-Hydroxybenzoic Acid in Xanthine Oxidase Inhibition

Chin, Yong Sin (2020) A Study on the Interaction Between Kaempferol, Apigenin and 4-Hydroxybenzoic Acid in Xanthine Oxidase Inhibition. Final Year Project (Bachelor), Tunku Abdul Rahman University College.

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Abstract

Xanthine oxidase (XO) is a biological enzyme takes part in purine catabolism. It catalyzes hypoxanthine to xanthine and eventually xanthine to uric acid in human bloodstream. The catabolism reaction increases the level of uric acid and this result in hyperuricemia. Allopurinol is a XO inhibitor that is used clinically to prevent purine catabolism. Although it is an effective XO inhibitor, it causes some side effects such as hypersensitivity syndrome, impaired liver function and renal toxicity. Therefore, a more effective inhibitor with fewer side effects needs to be invented. In the past, people believe that traditional Chinese medicine can cure many diseases. Chrysanthemum morifolium Ramat. has been demonstrated to contain phenolic compounds which are potent inhibitors of XO. In this study, in silico and in vitro study were conducted to investigate the interaction between potential inhibitors such as apigenin, kaempferol and 4-hydroxybenzoic acid on XO inhibition. In this study, apigenin showed the highest inhibitory activity of 73.6% among the compounds tested. Our results showed the highest XO inhibitory activity of 73.6% in apigenin among the compounds tested. Interaction assay demonstrated additive interaction between apigenin with kaempferol (or 4-hydroxybenzoic acid) and also kaempferol with 4-hydroxybenzoic acid. For molecular docking, apigenin was shown to have the best docking score of -8.2 kcal/mol, indicating its favorable interaction with XO. The in vitro additive interaction among the compounds tested was confirmed further via the multiple ligands docking simulation, indicated the independent ligands bound to the active site at non-interfering regional location. In summary, the combination of these three compounds can be explored further for their additive interaction in XO inhibition, which could be beneficial in terms of the enhanced effectiveness and lowered side effects when each is used at lower dose to give the same effect.