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Hypouricaemic action of mangiferin results from metabolite norathyriol via inhibiting xanthine oxidase activity.
Pharm Biol. 2016 Sep; 54(9):1680-6.PB

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 time-course study, mice received mangiferin and norathyriol both at a single dose of 7.1 μmol/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 IC50 value of 44.6 μM, 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.

Authors+Show Affiliations

a Biomedical Engineering Research Center , Kunming Medical University , Kunming , PR China ;a Biomedical Engineering Research Center , Kunming Medical University , Kunming , PR China ;b State Key Laboratory of Phytochemistry and Plant Resources in West China , Kunming Institute of Botany, Chinese Academy of Sciences , Kunming , PR China.a Biomedical Engineering Research Center , Kunming Medical University , Kunming , PR China ;a Biomedical Engineering Research Center , Kunming Medical University , Kunming , PR China ;a Biomedical Engineering Research Center , Kunming Medical University , Kunming , PR China ;a Biomedical Engineering Research Center , Kunming Medical University , Kunming , PR China ;

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26916555

Citation

Niu, Yanfen, et al. "Hypouricaemic Action of Mangiferin Results From Metabolite Norathyriol Via Inhibiting Xanthine Oxidase Activity." Pharmaceutical Biology, vol. 54, no. 9, 2016, pp. 1680-6.
Niu Y, Liu J, Liu HY, et al. Hypouricaemic action of mangiferin results from metabolite norathyriol via inhibiting xanthine oxidase activity. Pharm Biol. 2016;54(9):1680-6.
Niu, Y., Liu, J., Liu, H. Y., Gao, L. H., Feng, G. H., Liu, X., & Li, L. (2016). Hypouricaemic action of mangiferin results from metabolite norathyriol via inhibiting xanthine oxidase activity. Pharmaceutical Biology, 54(9), 1680-6. https://doi.org/10.3109/13880209.2015.1120322
Niu Y, et al. Hypouricaemic Action of Mangiferin Results From Metabolite Norathyriol Via Inhibiting Xanthine Oxidase Activity. Pharm Biol. 2016;54(9):1680-6. PubMed PMID: 26916555.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypouricaemic action of mangiferin results from metabolite norathyriol via inhibiting xanthine oxidase activity. AU - Niu,Yanfen, AU - Liu,Jia, AU - Liu,Hai-Yang, AU - Gao,Li-Hui, AU - Feng,Guo-Hua, AU - Liu,Xu, AU - Li,Ling, Y1 - 2016/02/26/ PY - 2016/2/27/entrez PY - 2016/2/27/pubmed PY - 2017/2/14/medline KW - Active metabolite KW - hyperuricaemia KW - structure–activity relationship KW - uric acid production SP - 1680 EP - 6 JF - Pharmaceutical biology JO - Pharm Biol VL - 54 IS - 9 N2 - 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 time-course study, mice received mangiferin and norathyriol both at a single dose of 7.1 μmol/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 IC50 value of 44.6 μM, 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. SN - 1744-5116 UR - https://www.unboundmedicine.com/medline/citation/26916555/Hypouricaemic_action_of_mangiferin_results_from_metabolite_norathyriol_via_inhibiting_xanthine_oxidase_activity_ L2 - http://www.tandfonline.com/doi/full/10.3109/13880209.2015.1120322 DB - PRIME DP - Unbound Medicine ER -