title: The molecular insight into the antihyperuricemic and renoprotective effect of Shuang Qi gout capsule in mice.
abstract: BACKGROUND
  Shuang-Qi gout capsule, a traditional Chinese medicine prescription, has been used in the treatment of, gout arthritis, arthralgia and inflammation. Since renal urate overload associated with severe disability including gout, elimination of excess renal uric acid is highly essential. Therefore, in this study we evaluated the antihyperuricemic and the renoprotective effect of the Shuang Qi gout capsule (SQ) with elucidation of its mechanism.
  
  
  METHODS
  We assessed the antihyperuricemic activity of SQ on urinary and serum uric acid, creatinine, blood urea nitrogen, fractional excretion of uric acid (FEUA) and glomerular filtration rate of creatinine and uric acid in potassium oxonate (PO) - induced mice as well as in non-induced mice. To illuminate the mechanism of antihyperuricemic activity, we investigated renal transport activity and the expression of mRNA levels in PO-induced and non-induced mice by western blot and RT-PCR methods.
  
  
  RESULTS
  SQ showed significant reduction in serum uric acid, creatinine and blood urea nitrogen levels and marked elevation of urine uric acid, creatinine and FEUA levels only in hyperuricemic mice. Furthermore, SQ could recover the altered expressions of proteins and mRNA levels of all the main renal transporters significantly in dose dependent manner.
  
  
  CONCLUSIONS
  SQ could effectively regulate the main renal transporters denoted its denote probable antihyperuricemic mechanism of SQ and its dose dependent uricosuric effect. In addition, SQ attenuated the deleterious effects of hyperuricemia with renal dysfunction. Thus SQ could be a potent antihyperuricemic agent which can perform as a safer and effective agent in the management of hyperuricemia via regulating the renal transporters.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Nandani Darshika
authors.initials: ND
authors.lastname: Kodithuwakku
authors.affiliation: Technology Center of Shenzhen Neptunus Bioengineering Co., Ltd, Shenzhen 518057, PR China.
authors.forename: Yi-dong
authors.initials: YD
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China.
authors.forename: Yan-yan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The Third People׳s Hospital of Changzhou, No. 300, Lanling North Road, Changzhou, Jiangsu, China.
authors.forename: Min
authors.initials: M
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: weirongfang@163.com.
authors.forename: Wei-rong
authors.initials: WR
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China. Electronic address: yunmanlicpu@hotmail.com.
authors.forename: Yun-man
authors.initials: YM
authors.lastname: Li
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001806:Blood Urea Nitrogen; D002214:Capsules; D002352:Carrier Proteins / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D006073:Gout / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D006074:Gout Suppressants / Q000494:pharmacology* / Q000627:therapeutic use; D033461:Hyperuricemia / Q000188:drug therapy / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008813:Mice, Inbred ICR; D027361:Organic Anion Transporters / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000378:metabolism; D010094:Oxonic Acid; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000074058:Solute Carrier Family 22 Member 5; 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; D002214:Capsules; D002352:Carrier Proteins; D004365:Drugs, Chinese Herbal; D006074:Gout Suppressants; D008565:Membrane Proteins; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D020011:Protective Agents; C000590845:Shuang-Qi; C109687:Slc22a12 protein, mouse; C491659:Slc22a4 protein, mouse; C492019:Slc22a5 protein, mouse; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D014527:Uric Acid; C489337:potassium oxonate; D010094:Oxonic Acid; D003404:Creatinine
keywords: Antihyperuricemic activity; Gout; Mice; Regulatory actions; Renal transporters; SQ gout capsule