摘要
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 IC_(50) values from 0.65 to 29.11μM.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 simula-tion.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 hydro-phobic 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.
基金
supported in part by the National Natural Science Foundation of China,China[grant number 82304613]
Qingdao City of Postdoctoral Program[grant number QDBSH20220202186]
Shandong Provincial Natural Science Foundation,China[grant number ZR2021QH085].
