Abstract: Mangiferin,a natural glucosyl xanthone,has been reported to possess a potential hypouricemic effect.However,the pharmacokinetic studies in rats showed that its oral bioavailability was only 1.2%,suggesting that mangiferin metabolites might exert the action.To screen the active constituent of mangiferin for hypouricemic action,two metabolites (2,3) and four precursors (4,5,6,7) were synthesized using 2,4,5-trimethoxybenzoic acid and 2,5-dimethoxybenzoic acid as starting material.Their structures were characterized by ¹H NMR and ¹³C NMR.Of the tested compounds,compound 2 (1,3,6,7-tetrahydroxyxanthone) exhibited a significant inhibitory activity on xanthine oxidase with an IC₅₀ value of 10.89 μM.Compound 3 (1,3,7-trihydroxyxanthone),the precursors 5 and 7 also inhibited the enzymatic activities at a concentration of 87.3 μM,with the inhibitory rates of 45.8%,52.1% and 32.1%,respectively.However,the inhibition effects of other precursors and mangiferin was not observed. In vivo,intragastric administration of mangiferin (1) and compound 2 significantly reduced the serum urate levels in hyperuricemic mice induced by potassium oxonate,compared with the untreated hyperuricemic mice (P<0.05).The hypouricemic action of compound 2 was similar in potency to mangiferin (1) at a same molar dose.These findings suggested that the hypouricemic effect of mangiferin was related to its metabolites,at least partly resulting from compound 2,via inhibiting xanthine oxidase activity.

Key words: mangiferin, metabolites, synthesis, xanthine oxidase, hyperuricemia