• Title/Summary/Keyword: Urate transporter

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Saengmaeksan, a traditional herbal formulation consisting of Panax ginseng, ameliorates hyperuricemia by inhibiting xanthine oxidase activity and enhancing urate excretion in rats

  • Sung, Yoon-Young;Yuk, Heung Joo;Kim, Dong-Seon
    • Journal of Ginseng Research
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    • v.45 no.5
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    • pp.565-574
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    • 2021
  • Background: Saengmaeksan (SMS) is a traditional Korean medicine composed of three herbs, Panax ginseng, Schisandra chinensis, and Liriope platyphylla. SMS is used to treat respiratory and cardiovascular disorders. However, whether SMS exerts antihyperuricemic effects is unknown. Methods: Effects of the SMS extract in water (SMS-W) and 30% ethanol (SMS-E) were studied in a rat model of potassium oxonate-induced hyperuricemia. Uric acid concentrations and xanthine oxidase (XO) activities were evaluated in the serum, urine, and hepatic tissue. Using renal histopathology to assess kidney function and uric acid excretion, we investigated serum creatinine and blood urea nitrogen concentrations, as well as protein levels of renal urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), and organic anion transporter 1 (OAT1). The effects of SMS on in vitro XO activity and uric acid uptake were also evaluated. The components of SMS were identified using Ultra Performance Liquid Chromatography (UPLC). Results: SMS-E reduced serum uric acid and creatinine concentrations, and elevated urine uric acid excretion. SMS-E lowered XO activities in both the serum and liver, and downregulated the expression of renal URAT1 and GLUT9 proteins. SMS-E reduced renal inflammation and IL-1b levels in both the serum and kidneys. SMS-E inhibited both in vitro XO activity and urate uptake in URAT1-expressing oocytes. Using UPLC, 25 ginsenosides were identified, all of which were present in higher levels in SMS-E than in SMS-W. Conclusion: SMS-E exhibited antihyperuricemic effects by regulating XO activity and renal urate transporters, providing the first evidence of its applicability in the treatment of hyperuricemia and gout.

A case of idiopathic renal hypouricemia (신성 저요산혈증 1례)

  • Han, Moon Hee;Park, Sang Uk;Kim, Deok-Soo;Shim, Jae Won;Shim, Jung Yeon;Jung, Hye Lym;Park, Moon Soo
    • Clinical and Experimental Pediatrics
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    • v.50 no.5
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    • pp.489-492
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    • 2007
  • Idiopathic renal hypouricemia is a disorder characterized by impaired urate handling in the renal tubules. This disease usually produces no symptoms, but hematuria, uric acid nephrolithiasis or acute renal failure may develop. A defect in the SLC22A12 gene, which encodes the human urate transporter, is the known major cause of this disorder. We describe a 10-month-old boy with idiopathic renal hypouricemia. He was diagnosed with transient pseudohypoaldosteronism at admission, but hypouricemia was accidentally found through follow-up study. By gene analysis, his diagnosis was confirmed to idiopathic renal hypouricemia. In addition, we report a mutation in the human urate transporter 1 (hURAT1) gene identified in his family.

Hyperuricemic effects of Alpiniae Oxyphyllae Fructus extracts (고요산동물에서의 익지인의 요산저하 효과)

  • Lee, Young-Sil;Kim, Jiyoun;Kim, Seung-Hyung;Kim, Dong-Seon
    • The Korea Journal of Herbology
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    • v.32 no.6
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    • pp.23-29
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    • 2017
  • Objective : Hyperuricemia is a metabolic disease characterized by elevated blood uric acid levels, and its prevalence is rapidly increasing worldwide. Alpiniae Oxyphyllae Fructus (AO) belonging to Zingiberaceae is one of well-known traditional medicines in China and Korea, and has been used to treat intestinal disorders, urosis, diuresis, and chronic glomerulonephritis traditionally. However, the effect of AO has not been studied. In this study we investigated the anti-hyperuricemic effect of AO, and the mechanisms underlying the effect in potassium oxonate (PO)-induced hyperuricemic rats. Methods : To examine the anti-hyperuricemic effects of the AO extract, serum uric acid levels were analyzed in normal and PO-induced hyperuricemic rats. The mechanism underlying the effects of the AO extract on uric acid levels was studied through xanthine oxidase (XOD) activity test and uric acid uptake assay in vitro. The chemical finger printing of the AO extract was analyzed using HPLC-DAD. Results : The AO extract significantly reduced serum uric acid levels in normal as well as PO-induced hyperuricemic rats. It also significantly inhibited the uptake of uric acid in oocytyes and human embryonic kidney cells (HEK293) expressing urate transporter (URAT)1, but not XOD activity in vitro. The chemical finger printing analysis of the AO extract showed nootkatone as a main component. Conclusion : The AO extract exhibits anti-hyperuricemic effects, and these effect were accompanied by increasing excretion of uric acid in kidney. Therefore, the AO extract could be used for prevention or treatment of hyperuicemia and gout.

Development of High-specificity Antibodies against Renal Urate Transporters Using Genetic Immunization

  • Xu, Guoshuang;Chen, Xiangmei;Wu, Di;Shi, Suozhu;Wang, Jianzhong;Ding, Rui;Hong, Quan;Feng, Zhe;Lin, Shupeng;Lu, Yang
    • BMB Reports
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    • v.39 no.6
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    • pp.696-702
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    • 2006
  • Recently three proteins, playing central roles in the bidirectional transport of urate in renal proximal tubules, were identified: two members of the organic anion transporter (OAT) family, OAT1 and OAT3, and a protein that designated renal urate-anion exchanger (URAT1). Antibodies against these transporters are very important for investigating their expressions and functions. With the cytokine gene as a molecular adjuvant, genetic immunization-based antibody production offers several advantages including high specificity and high recognition to the native protein compared with current methods. We fused high antigenicity fragments of the three transporters to the plasmids pBQAP-TT containing T-cell epitopes and flanking regions from tetanus toxin, respectively. Gene gun immunization with these recombinant plasmids and two other adjuvant plasmids, which express granulocyte/macrophage colony-stimulating factor and FMS-like tyrosine kinase 3 ligand, induced high level immunoglobulin G antibodies, respectively. The native corresponding proteins of URAT1, OAT1 and OAT3, in human kidney can be recognized by their specific antibodies, respectively, with Western blot analysis and immunohistochemistry. Besides, URAT1 expression in Xenopus oocytes can also be recognized by its corresponding antibody with immuno-fluorescence. The successful production of the antibodies has provided an important tool for the study of UA transporters.