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        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

        Junxia Su,Yu-Hui Wei,Minglong Liu,Tianxi Liu,Jianhua Li,Yuanchun Ji,Jianping Liang 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.10

        Rhizoma Dioscoreae septemlobae (RDSE) hasbeen widely used for the treatment of hyperuricemia inChina. However, the therapeutic mechanism has beenunknown. This study investigated the antihyperuricemicmechanisms of the extracts obtained from RDSE and itsmain component dioscin (DIS) in hyperuricemic mice. Hyperuricemic mice were induced by potassium oxonate(250 mg/kg). RDSE or DIS was orally administered tohyperuricemic mice at dosages of 319.22, 638.43,1276.86 mg/kg/day for 10 days, respectively. Uric acid orcreatinine in serum and urine was determined by HPLC orHPLC–MS/MS, respectively. The xanthine oxidase (XO)activities in mice liver were examined in vitro. Proteinlevels of organic anion transporter 1 (mOAT1), uratetransporter 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 serumwere significantly increased by potassium oxonate, ascompared to that of control mice. Compared saline-treatedgroup, after RDSE treatment in the high and middle dose,the expression of mOAT1 increased 47.98 and 54.48 %,respectively, which accompanied with the decreasedexpression of mURAT1 (47.63 %) in high dose. After DIS treatment in high, middle and low dose, the expression ofmOAT1 increased 23.93, 32.80 and 25.28 % compared tosaline-treated group, respectively, which accompanied withthe decreased expression of mURAT1 (51.07, 51.42 and51.35 %). However, RDSE and DIS displayed a weak XOinhibition activity compared with allopurinol. Therefore,RDSE and DIS processed uricosuric and nephroprotectiveactions by regulation of mOAT1, mURAT1 and mOCT2.

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