title: Antihyperuricemic and nephroprotective effects of resveratrol and its analogues in hyperuricemic mice.
abstract: METHODS
  Stilbenes, of which, resveratrol is a representative compound in foods and plants, possess a variety of bioactivities including antioxidation, anti-inflammation, chemoprevention, and cardioprotection. This study was conducted to evaluate the antihyperuricemic and nephroprotective effects of resveratrol and its analogues and explore the possible mechanisms. The structure-activity relationships were analyzed.
  
  
  RESULTS
  Potassium oxonate-induced hyperuricemic mice were dosed by gavage with eight stilbenes. Uric acid, creatinine, and blood urea nitrogen (BUN) levels in serum and urine, clearance rate of creatinine and BUN, 24-h urate excretion, and fractional excretion of uric acid, uromodulin levels in urine and kidney were determined to evaluate renal urate handling and function. Renal protein levels of organic ion transporters were detected to elucidate the possible mechanisms. Resveratrol, trans-4-hydroxystilbene, pterostilbene, polydatin, and mulberroside A were found to have antihyperuricemic activities. These compounds together with trans-2-hydroxystilbene provided nephroprotection. Trans-3,4',5-trimethoxystilbene and cis-combretastatin A-4 had no effects.
  
  
  CONCLUSIONS
  The uricosuric and nephroprotective actions of resveratrol and its analogues were mediated by regulating renal organic ion transporters in hyperuricemic mice, supporting their beneficial effects for the prevention of hyperuricemia. The number and position, methoxylation and glycosylation of hydroxyl groups in these trans-stilbenes were required for their effects.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, PR China.
authors.forename: Yun-Wei
authors.initials: YW
authors.lastname: Shi
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Yang-Liu
authors.initials: YL
authors.lastname: Liu
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Hong
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Kong
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001806:Blood Urea Nitrogen; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003404:Creatinine / Q000097:blood / Q000652:urine; D004187:Disaccharides / Q000494:pharmacology; D005786:Gene Expression Regulation; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics / Q000378:metabolism; D005960:Glucosides / Q000494:pharmacology; D006074:Gout Suppressants / Q000494:pharmacology*; D033461:Hyperuricemia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D050811:Octamer Transcription Factor-1 / Q000235:genetics / Q000378:metabolism; D027362:Organic Anion Transport Protein 1 / Q000235:genetics / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D000075102:Organic Cation Transporter 2; D010094:Oxonic Acid; D000077185:Resveratrol; D000074058:Solute Carrier Family 22 Member 5; D013267:Stilbenes / Q000494:pharmacology*; D027981:Symporters; D014527:Uric Acid / Q000097:blood / Q000652:urine
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D002352:Carrier Proteins; D004187:Disaccharides; D051246:Glucose Transport Proteins, Facilitative; D005960:Glucosides; D006074:Gout Suppressants; D008565:Membrane Proteins; D050811:Octamer Transcription Factor-1; D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; C494166:Pou2f1 protein, mouse; C109687:Slc22a12 protein, mouse; C491012:Slc22a2 protein, mouse; C491659:Slc22a4 protein, mouse; C492019:Slc22a5 protein, mouse; C105033:Slc22a6 protein, mouse; C498775:Slc2a9 protein, mouse; D000074058:Solute Carrier Family 22 Member 5; D013267:Stilbenes; D027981:Symporters; C420606:mulberroside A; C572671:trans-3,4'-dihydroxy-2',3',5-trimethoxystilbene; D014527:Uric Acid; C107773:pterostilbene; C489337:potassium oxonate; D010094:Oxonic Acid; C515052:trans-2,3',4,5'-tetrahydroxystilbene; D003404:Creatinine; C058728:fosbretabulin; D000077185:Resveratrol; C058229:polydatin