title: Anti-hyperuricemic and nephroprotective effects of Rhizoma Dioscoreae septemlobae extracts and its main component dioscin via regulation of mOAT1, mURAT1 and mOCT2 in hypertensive mice.
abstract: Rhizoma Dioscoreae septemlobae (RDSE) has been widely used for the treatment of hyperuricemia in China. However, the therapeutic mechanism has been unknown. This study investigated the antihyperuricemic mechanisms of the extracts obtained from RDSE and its main component dioscin (DIS) in hyperuricemic mice. Hyperuricemic mice were induced by potassium oxonate (250 mg/kg). RDSE or DIS was orally administered to hyperuricemic mice at dosages of 319.22, 638.43, 1276.86 mg/kg/day for 10 days, respectively. Uric acid or creatinine in serum and urine was determined by HPLC or HPLC-MS/MS, respectively. The xanthine oxidase (XO) activities in mice liver were examined in vitro. Protein levels of organic anion transporter 1 (mOAT1), urate transporter 1 (mURAT1) and organic cation transporter 2 (mOCT2) in the kidney were analyzed by western blotting. The results indicated that uric acid and creatinine in serum were significantly increased by potassium oxonate, as compared to that of control mice. Compared saline-treated group, after RDSE treatment in the high and middle dose, the expression of mOAT1 increased 47.98 and 54.48 %, respectively, which accompanied with the decreased expression of mURAT1 (47.63 %) in high dose. After DIS treatment in high, middle and low dose, the expression of mOAT1 increased 23.93, 32.80 and 25.28 % compared to saline-treated group, respectively, which accompanied with the decreased expression of mURAT1 (51.07, 51.42 and 51.35 %). However, RDSE and DIS displayed a weak XO inhibition activity compared with allopurinol. Therefore, RDSE and DIS processed uricosuric and nephroprotective actions by regulation of mOAT1, mURAT1 and mOCT2.
authors.affiliation: College of Veterinary Medicine, Gansu Agriculture University, Lanzhou, 730070, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Su
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Wei
authors.forename: Minglong
authors.initials: M
authors.lastname: Liu
authors.forename: Tianxi
authors.initials: T
authors.lastname: Liu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.forename: Yuanchun
authors.initials: Y
authors.lastname: Ji
authors.forename: Jianping
authors.initials: J
authors.lastname: Liang
mesh_terms: D000818:Animals; D003404:Creatinine / Q000097:blood / Q000652:urine; D027742:Dioscorea / Q000737:chemistry*; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D033461:Hyperuricemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D027362:Organic Anion Transport Protein 1 / Q000096:biosynthesis*; D027361:Organic Anion Transporters / Q000096:biosynthesis*; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis*; D000075102:Organic Cation Transporter 2; D010094:Oxonic Acid; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D027343:Rhizome / Q000737:chemistry; D014527:Uric Acid / Q000097:blood / Q000652:urine; D014969:Xanthine Oxidase / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D000075102:Organic Cation Transporter 2; D010936:Plant Extracts; C109687:Slc22a12 protein, mouse; C491012:Slc22a2 protein, mouse; C105033:Slc22a6 protein, mouse; D014527:Uric Acid; C019357:dioscin; C489337:potassium oxonate; D010094:Oxonic Acid; D003404:Creatinine; D014969:Xanthine Oxidase; D004144:Diosgenin