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Hypouricemic and Nephroprotective Effects of Emodinol in Oxonate-Induced Hyperuricemic Mice are Mediated by Organic Ion Transporters and OIT3.
Planta Med. 2016 Mar; 82(4):289-297.PM

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+Show Affiliations

School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China.State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.School of Pharmacy, China Pharmaceutical University, Nanjing, P. R. China. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, P. R. China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26584455

Citation

Hui, Wu, et al. "Hypouricemic and Nephroprotective Effects of Emodinol in Oxonate-Induced Hyperuricemic Mice Are Mediated By Organic Ion Transporters and OIT3." Planta Medica, vol. 82, no. 4, 2016, pp. 289-297.
Hui W, Yongliang Y, Yongde C, et al. Hypouricemic and Nephroprotective Effects of Emodinol in Oxonate-Induced Hyperuricemic Mice are Mediated by Organic Ion Transporters and OIT3. Planta Med. 2016;82(4):289-297.
Hui, W., Yongliang, Y., Yongde, C., Guo, L., Li, L., Zhonglin, Y., Hui, J., & Qinghua, H. (2016). Hypouricemic and Nephroprotective Effects of Emodinol in Oxonate-Induced Hyperuricemic Mice are Mediated by Organic Ion Transporters and OIT3. Planta Medica, 82(4), 289-297. https://doi.org/10.1055/s-0035-1558212
Hui W, et al. Hypouricemic and Nephroprotective Effects of Emodinol in Oxonate-Induced Hyperuricemic Mice Are Mediated By Organic Ion Transporters and OIT3. Planta Med. 2016;82(4):289-297. PubMed PMID: 26584455.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypouricemic and Nephroprotective Effects of Emodinol in Oxonate-Induced Hyperuricemic Mice are Mediated by Organic Ion Transporters and OIT3. AU - Hui,Wu, AU - Yongliang,Yuan, AU - Yongde,Chen, AU - Guo,Lu, AU - Li,Lan, AU - Zhonglin,Yang, AU - Hui,Ji, AU - Qinghua,Hu, Y1 - 2015/11/19/ PY - 2015/11/20/entrez PY - 2015/11/20/pubmed PY - 2016/11/1/medline SP - 289 EP - 297 JF - Planta medica JO - Planta Med. VL - 82 IS - 4 N2 - 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. SN - 1439-0221 UR - https://www.unboundmedicine.com/medline/citation/26584455/Hypouricemic_and_Nephroprotective_Effects_of_Emodinol_in_Oxonate_Induced_Hyperuricemic_Mice_are_Mediated_by_Organic_Ion_Transporters_and_OIT3_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-0035-1558212 DB - PRIME DP - Unbound Medicine ER -