title: Mangiferin Inhibits Renal Urate Reabsorption by Modulating Urate Transporters in Experimental Hyperuricemia.
abstract: Mangiferin, a natural glucosyl xanthone from the leaves of Mangifera indica L., was previously shown to exert potent hypouricemic effects associated with inhibition of the activity of xanthine dehydrogenase/oxidase. The present study aimed to evaluate its uricosuric effect and possible molecular mechanisms underlying the renal urate transporters responsible for urate reabsorption in vivo. Mangiferin (1.5-24.0 mg/kg) was administered intragastrically to hyperuricemic mice and rats induced by the intraperitoneal injection of uric acid and potassium oxonate, respectively. The uricosuric effect was evaluated by determining the serum and urinary urate levels as well as fractional excretion of uric acid (FEUA). The mRNA and protein levels of renal urate-anion transporter 1 (URAT1), organic anion transporter 10 (OAT10), glucose transporter 9 (GLUT9), and PDZ domain-containing protein (PDZK1) were analyzed. The administration of mangiferin significantly decreased the serum urate levels in hyperuricemic mice in a dose- and time-dependent manner. In hyperuricemic rats, mangiferin also reduced the serum urate levels and increased the urinary urate levels and FEUA. These results indicate that mangiferin has uricosuric effects. Further examination showed that mangiferin markedly inhibited the mRNA and protein expression of renal URAT1, OAT10, and GLUT9 in hyperuricemic rats, but did not interfere with PDZK1 expression. Taken together, these findings suggest that mangiferin promotes urate excretion by the kidney, which may be related to the inhibition of urate reabsorption via downregulation of renal urate transporters.
authors.affiliation: Biomedical Engineering Research Center, Kunming Medical University.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Lihui
authors.initials: L
authors.lastname: Gao
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Niu
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Hua
authors.initials: H
authors.lastname: Lin
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.forename: Xiangfu
authors.initials: X
authors.lastname: Kong
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins; D033461:Hyperuricemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism; D010094:Oxonic Acid; D017207:Rats, Sprague-Dawley; D014527:Uric Acid / Q000097:blood / Q000378:metabolism* / Q000652:urine; D014528:Uricosuric Agents / Q000494:pharmacology*; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D027321:Anion Transport Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C498776:GLUT6 protein, rat; D009004:Monosaccharide Transport Proteins; C109245:Pdzk1 protein, rat; C554079:Slc22a12 protein, rat; D014528:Uricosuric Agents; D044004:Xanthones; C013592:mangiferin; D014527:Uric Acid; C489337:potassium oxonate; D010094:Oxonic Acid