title: Mulberroside a possesses potent uricosuric and nephroprotective effects in hyperuricemic mice.
abstract: Mulberroside A is a major stilbene glycoside of MORUS ALBA L. (Moraceae), which is effectively used for the treatment of hyperuricemia and gout in traditional Chinese medicine. We examined whether mulberroside A had effects on renal urate underexcretion and dysfunction in oxonate-induced hyperuricemic mice and investigated the potential uricosuric and nephroprotective mechanisms involved. Mulberroside A at 10, 20, and 40 mg/kg decreased serum uric acid levels and increased urinary urate excretion and fractional excretion of uric acid in hyperuricemic mice. Simultaneously, it reduced serum levels of creatinine and urea nitrogen (10-40 mg/kg), urinary N-acetyl- β-D-glucosaminidase activity (10-40 mg/kg), β₂-microglobulin (10-40 mg/kg) and albumin (20-40 mg/kg), and increased creatinine clearance (10-40 mg/kg) in hyperuricemic mice. Furthermore, mulberroside A downregulated mRNA and protein levels of renal glucose transporter 9 (mGLUT9) and urate transporter 1 (mURAT1), and upregulated mRNA and protein levels of renal organic anion transporter 1 (mOAT1) and organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1, and mOCTN2) in hyperuricemic mice. This is the first study demonstrating that mulberroside A exhibits uricosuric and nephroprotective effects mediated in part by cooperative attenuation of the expression alterations of renal organic ion transporters in hyperuricemic mice. These data suggest that mulberroside A may be a new drug candidate for the treatment of hyperuricemia with renal dysfunction.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, P. R. China.
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Wang
authors.forename: Yemin
authors.initials: Y
authors.lastname: Wang
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.forename: Xian
authors.initials: X
authors.lastname: Zhang
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Ye
authors.forename: Lin-Shui
authors.initials: LS
authors.lastname: Hu
authors.forename: Ling-Dong
authors.initials: LD
authors.lastname: Kong
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000419:Albuminuria / Q000652:urine; D000818:Animals; D001806:Blood Urea Nitrogen; D002352:Carrier Proteins / Q000096:biosynthesis; D003404:Creatinine / Q000097:blood; D004187:Disaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D033461:Hyperuricemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D031625:Morus / Q000737:chemistry; D027362:Organic Anion Transport Protein 1 / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis; D000075102:Organic Cation Transporter 2; D020011:Protective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000074058:Solute Carrier Family 22 Member 5; D013267:Stilbenes / Q000302:isolation & purification / Q000494:pharmacology*; D027981:Symporters; D014527:Uric Acid / Q000097:blood / Q000652:urine; D014528:Uricosuric Agents / Q000494:pharmacology*; D001613:beta 2-Microglobulin / Q000652:urine
chemical_list: D002352:Carrier Proteins; D004187:Disaccharides; D004365:Drugs, Chinese Herbal; D051246:Glucose Transport Proteins, Facilitative; D008565:Membrane Proteins; D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D020011:Protective Agents; 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; D014528:Uricosuric Agents; D001613:beta 2-Microglobulin; C420606:mulberroside A; D014527:Uric Acid; D003404:Creatinine; D000118:Acetylglucosaminidase