Identification of aurones and chalcones as the main contributors to xanthine oxidase inhibitory activity of snow chrysanthemum

Abstract

Snow chrysanthemum, the capitulum of Coreopsis tinctoria Nutt., was found to possess inhibitory activity on xanthine oxidase (XO), one of the key enzymes in the pathogenesis of gout. Assisted by bioactivity-oriented isolation, a total of 16 compounds containing a new compound were obtained from the active fractions of snow chrysanthemum extract, including two aurones (1, 2), four chalcones (3–6), a flavone (7), four flavonols (8-11), a flavanonol (12), three phenylpropanoids (13–15), and a new polyacetylene glycoside (16). All the isolated compounds were assayed for their inhibitory activity on XO, among which eight polyphenols (1–8) exhibited potent or moderate inhibitory activities with IC50 values from 0.65 to 29.11 μM. The structure-activity relationship was interpreted for polyphenols (1-12). Besides, the inhibition properties of compounds 1–4 against XO were comprehensively investigated through enzyme kinetics, fluorescence quenching, and docking simulation. Maritimetin (1) and sulfurein (2) reversibly inhibited XO by mixed type mechanism. Okanin-4′-O-(6″-acetyl)-β-d-glucopyranoside (3) and coreopsin (4) competitively inhibited XO in reversible and irreversible manners, respectively. In addition, fluorescence quenching studies suggested that all four compounds interacted with XO through a static quenching mechanism. Molecular docking inferred that hydrogen bonds and hydrophobic interaction played key roles in the binding process. This study revealed the XO-inhibitory activity of snow chrysanthemum and the contribution of containing aurones and chalcones to XO inhibition, making it a potential functional food ingredient for management of hyperuricemia.