Hypouricaemic action of mangiferin results from metabolite norathyriol via inhibiting xanthine oxidase activity

Abstract

Context Mangiferin has been reported to possess a potential hypouricaemic effect. However, the pharmacokinetic studies in rats showed that its oral bioavailability was only 1.2%, suggesting that mangiferin metabolites might exert the action. Objective The hypouricaemic effect and the xanthine oxidase inhibition of mangiferin and norathyriol, a mangiferin metabolite, were investigated. Inhibition of norathyriol analogues (compounds 3-9) toward xanthine oxidase was also evaluated. Materials and methods For a dose-dependent study, mangiferin (1.5-6.0 mg/kg) and norathyriol (0.92-3.7 mg/kg) were administered intragastrically to mice twice daily for five times. For a timecourse study, mice received mangiferin and norathyriol both at a single dose of 7.1 mmol/kg. In vitro, inhibition of test compounds (2.4-2.4 mM) against xanthine oxidase activity was evaluated by the spectrophotometrical method. The inhibition type was identified from Lineweaver-Burk plots. Results Norathyriol (0.92, 1.85 and 3.7 mg/kg) dose dependently decreased the serum urate levels by 27.0, 33.6 and 37.4%, respectively. The action was more potent than that of mangiferin at the low dose, but was equivalent at the higher doses. Additionally, the hypouricaemic action of them exhibited a time dependence. In vitro, norathyriol markedly inhibited the xanthine oxidase activities, with the IC 50 value of 44.6 mM, but mangiferin did not. The kinetic studies showed that norathyriol was an uncompetitive inhibitor by Lineweaver-Burk plots. The structure-activity relationships exhibited that three hydroxyl groups in norathyriol at the C-1, C-3 and C-6 positions were essential for maintaining xanthine oxidase inhibition. Discussion and conclusion Norathyriol was responsible for the hypouricaemic effect of mangiferin via inhibiting xanthine oxidase activity. ARTICLE HISTORY

Mangifera indica L. Leaf Extract in Combination With Luteolin or Quercetin Enhances VO2peak and Peak Power Output, and Preserves Skeletal Muscle Function During Ischemia-Reperfusion in Humans

“…The three polyphenols tested here have free radical quenching capacity (González-Gallego et al, 2010 ; Braakhuis and Hopkins, 2015 ; Luo et al, 2017 ; Rauf et al, 2017 ), being also inhibitors of XO (Pinto et al, 2005 ; Paredes-Gonzalez et al, 2015 ; Niu et al, 2016 ) and NOX (Makino et al, 2013 ; Xia N. et al, 2014 ). However, no study in humans has shown that antioxidants, even when administered intravenously are capable of enhancing peak power output during repeated prolonged sprint exercise.…”

“…Luteolin (30, 40, 50, 70-tetrahydroxyflavone) is one of the most abundant flavones and, like mangiferin and quercetin, is a potent antioxidant and inhibitor of xanthine oxidase (XO) (Nagao et al, 1999 ; Pinto et al, 2005 ; Paredes-Gonzalez et al, 2015 ; Niu et al, 2016 ; Nile et al, 2017 ). Luteolin is also a NADPH oxidase (nicotinamide adenine dinucleotide phosphate-oxidase; NOX) inhibitor (Makino et al, 2013 ; Xia F. et al, 2014 ).…”

Enhancement of Exercise Performance by 48 Hours, and 15-Day Supplementation with Mangiferin and Luteolin in Men

“…Natural polyphenols like mangiferin and luteolin are potent antioxidants and inhibitors of XO [23,38,39] and NOX [40,41]. A previous study has shown ergogenic effects after acute supplementation (48 h) with a mango leave extract (MLE, Zynamite ® ) combined with either quercetin or luteolin [27].…”

Supplementation with a Mango Leaf Extract (Zynamite®) in Combination with Quercetin Attenuates Muscle Damage and Pain and Accelerates Recovery after Strenuous Damaging Exercise

“…Mangiferin (2-bD-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone) is a xanthone abundant in the leaf and pulp of mangoes, which is also present in other edible vegetables [20]. Mangiferin has iron-chelating properties, free-radical scavenging capacity and inhibits some of the oxidases involved in oxidative stress and inflammation [7,9,[21][22][23][24]. For these reasons, a natural extract rich in mangiferin may mitigate or prevent EIMD.…”