title: Hypouricemic and Nephroprotective Effects of Emodinol in Oxonate-Induced Hyperuricemic Mice are Mediated by Organic Ion Transporters and OIT3.
abstract: Emodinol, 1β,3β,23-trihydroxyolean-12-en-28-acid, as the main active ingredient firstly extracted from the rhizomes of Elaeagus pungens by our research group, has been demonstrated to exhibit uricosuric activity by our previous study. The aim of this study was to evaluate the uricosuric and nephroprotective effects of emodinol and explore its possible mechanisms in potassium oxonate-induced hyperuricemic mice with renal dysfunction. Mice were orally administrated 250 mg/kg of potassium oxonate once daily for 7 consecutive days to induce hyperuricemia with renal dysfunction. Emodinol was given at doses of 25, 50, and 100 mg/kg on the same day 1 h after oxonate treatment, and allopurinol (10 mg/kg) was given as a positive control. After 1 week, serum uric acid, serum creatinine, urine uric acid, urine creatinine, blood urea nitrogen, and hepatic xanthine oxidase activity were determined. The mRNA and protein levels of urate transporter 1, glucose transporter 9, ATP-binding cassette subfamily G member 2, organic anion transporter 1, oncoprotein-induced transcript 3, and organic cation/carnitine transporters in the kidney were detected by real-time polymerase chain reaction and Western blot analysis. In addition, urinary and renal Tamm-Horsfall glycoprotein concentrations were examined by ELISA assays. Emodinol significantly reduced serum urate levels, increased urinary urate levels and fractional excretion of uric acid, and inhibited hepatic xanthine oxidase activity in hyperuricemic mice. Moreover, potassium oxonate administration led to dys expressions of renal urate transporter 1, glucose transporter 9, ATP-binding cassette subfamily G member 2, organic anion transporter 1, and oncoprotein-induced transcript 3 as well as alternations of uromodulin concentrations, which could be reversed by emodinol. On the other hand, treatment of emodinol caused upregulated expressions of organic cation/carnitine transporters, resulting in an improvement of renal function characterized by decreased serum creatinine and blood urea nitrogen levels. Emodinol exhibited hypouricemic and nephroprotective actions by inhibiting xanthine oxidase activity and regulating renal ion transporters and oncoprotein-induced transcript 3, which may be a potential therapeutic agent in hyperuricemia and renal dysfunction.
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Wu
authors.initials: W
authors.lastname: Hui
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yongliang
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yongde
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Guo
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhonglin
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Ji
authors.initials: J
authors.lastname: Hui
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: Hu
authors.initials: H
authors.lastname: Qinghua
mesh_terms: D000818:Animals; D031263:Elaeagnaceae / Q000737:chemistry*; D033461:Hyperuricemia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D017136:Ion Transport; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D010094:Oxonic Acid; D020011:Protective Agents / Q000627:therapeutic use; D011507:Proteinuria / Q000188:drug therapy; D014527:Uric Acid / Q000097:blood
chemical_list: C478118:1beta, 3beta, 23-trihydroxyolean-12-en-28-oic acid; C492692:LZP protein, mouse; D008565:Membrane Proteins; D020011:Protective Agents; D014527:Uric Acid; C489337:potassium oxonate; D010094:Oxonic Acid; D009828:Oleanolic Acid