Abstract
Xanthine oxidase (XO) plays an important role in purine degradation in humans. The study aimed to determine the XO inhibitory potential of Chrysanthemum morifolium dried flower ethyl acetate sub-fractions and its anti-hyperuricemic effect in rat models. Bioassay-guided fractionation based on XO inhibitory assay was employed to obtain bioactive fractions and sub-fractions. In vitro cytotoxicity and cellular antioxidant capacity of the sub-fraction and its mode of XO inhibition were also investigated. The anti-hyperuricemic effect of the bioactive sub-fraction was investigated using rat models via oral consumption, and followed by an XO mRNA gene expression study. The compounds in the bioactive sub-fractions were identified putatively using HPLC-Q-TOF-MS/MS. Ethyl acetate (EtOAc) fraction exhibited the highest XO inhibition among the fractions. It was further fractionated into 15 sub-fractions. F10 exhibited high XO inhibitory activity, cellular pro-proliferative effect, and intracellular antioxidant activity among the sub-fractions tested. This sub-fraction was non-cytotoxic at 0.1–10 µg/mL, and very effective in lowering serum and urine uric acid level in rat models upon oral consumption. A total of 26 known compounds were identified and seven unknown compounds were detected via HPLC-Q-TOF–MS/MS analysis. The possible mechanisms contributing to the anti-hyperuricemic effect were suggested to be the non-competitive inhibition of XO enzyme, XO gene expression down-regulation, and the enhancement of uric acid excretion.
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