The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Yanwen Zhang - One of the best experts on this subject based on the ideXlab platform.
-
pallidifloside d from smilax riparia enhanced allopurinol effects in Hyperuricemia mice
Fitoterapia, 2015Co-Authors: Piyong Hou, Jun Zhang, Shuqing Wang, Samantha Anderson, Yanwen ZhangAbstract:Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to be effective in hyperuricemic control. Allopurinol is a commonly used medication to treat Hyperuricemia and its complications. In this study, we evaluated whether Pallidifloside D could enhance allopurinol’s effects by decreasing the serum uric acid level in a hyperuricemic mouse model induced by potassium oxonate. We found that, compared with allopurinol alone, the combination of allopurinol and Pallidifloside D significantly decreased the serum uric acid level and increased the urine uric acid level (both P<0.05), leading to the normalized serum and urine uric acid concentrations. Data on serum, urine creatinine and BUN supported these observations. Our results showed that the synergistic effects of allopurinol combined with Pallidifloside D was linked to the inhibition of both serum and hepatic xanthine oxidase (XOD), the down-regulation of renal mURAT1 and mGLUT9, and the up-regulation of mOAT1. Our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions.
-
anti Hyperuricemia effects of allopurinol are improved by smilax riparia a traditional chinese herbal medicine
Journal of Ethnopharmacology, 2015Co-Authors: Chongzhi Wang, Jun Zhang, Shuqing Wang, Yanwen Zhang, Samantha Anderson, Chunsu YuanAbstract:Abstract Ethnopharmacological relevance The roots and rhizomes of Smilax riparia are called “Niu-Wei-Cai” in traditional Chinese medicine (TCM). This botanical has been used in treating the symptoms of gout and other hyperuricemic-related conditions in TCM. Allopurinol is a commonly used medication to treat Hyperuricemia and its complications. In this study, we evaluated whether Smilax riparia could enhance allopurinol׳s effects by decreasing the serum uric acid level in a hyperuricemic mouse model induced by potassium oxonate. Materials and methods We examined the effects of allopurinol (5 mg/kg) administration alone or in combination with Smilax riparia saponins (SRS, 500 mg/kg) on the serum uric acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels in a hyperuricemic mouse model. The effects of allopurinol alone or those of allopurinol plus SRS on the XOD activities were measured. Western blot analysis was used to measure the levels of mURAT1, mGLUT9 and mOTA1 in the mice. Results Compared with allopurinol alone, the combination of allopurinol and SRS significantly decreased the serum uric acid level and increased the urine uric acid level (both P Conclusion The anti-Hyperuricemia effects of allopurinol are improved by Smilax riparia co-administration. The results were supported by the measurement of uric acid, creatinine, BUN, XOD, mURAT1, mGLUT9 and mOAT1. Our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions.
-
pallidifloside d a saponin glycoside constituent from smilax riparia resist to Hyperuricemia based on urat1 and glut9 in hyperuricemic mice
Journal of Ethnopharmacology, 2014Co-Authors: Jinlan Ruan, Jun Zhang, Shuqing Wang, Yanwen ZhangAbstract:Abstract Ethnopharmacological relevance The roots and rhizomes of Smilax riparia (SR), called “Niu-Wei-Cai” in traditional Chinese medicine (TCM), are believed to be effective in treating Hyperuricemia and gout symptoms. This study was designed to isolate a saponin glycoside named pallidifloside D from the total saponins of Smilax riparia and to examine its effect in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. Materials and methods We examined the effects of pallidifloside D treated with 5, 10 and 20 mg/kg on serum uric acid levels (SUA), Serum creatinine (SCr) and blood urea nitrogen (BUN) levels in a hyperuricemic mouse. A colorimetric method was used to evaluate the effects of pallidifloside D on the XOD activities, and Western Blotting analysis were carried out to observe protein levels of mURAT1, mGLUT9 and mOTA1 in hyperuricemic mice after treatment with pallidifloside D. Results The levels of serum uric acid levels (SUA) were suppressed significantly with dose-dependence by pallidifloside D treated with 5, 10 and 20 mg/kg (p Conclusion These results suggest that pallidifloside D possesses a potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1 and GLUT9, which contribute to the enhancement of uric acid excretion and attenuate Hyperuricemia-induced renal dysfunction.
-
riparoside b and timosaponin j two steroidal glycosides from smilax riparia resist to Hyperuricemia based on urat1 in hyperuricemic mice
Phytomedicine, 2014Co-Authors: Jun Zhang, Shuqing Wang, Victor C Yang, Samantha Anderson, Yanwen ZhangAbstract:The roots and rhizomes of Smilax riparia (SR), called “Niu-Wei-Cai” in traditional Chinese medicine (TCM), are believed to be effective in treating gout symptoms. However, it is not clear if the active constituents and uricosuric mechanisms of S. riparia support its therapeutic activities. In this study, we isolated two steroidal glycosides named riparoside B and timosaponin J from the total saponins of S. riparia. We then examined if these two compounds were effective in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. We found that the two steroidal glycosides possess potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1 mainly and inhibiting XOD activity in a certain extent, which contribute to the enhancement of uric acid excretion and attenuate Hyperuricemia-induced renal dysfunction. Riparoside B and timosaponin J may have a clinical utility in treating gout and other medical conditions caused by Hyperuricemia.
Lingdong Kong - One of the best experts on this subject based on the ideXlab platform.
-
Morin Improves Urate Excretion and Kidney Function through Regulation of Renal Organic Ion Transporters in Hyperuricemic Mice
2016Co-Authors: Cai-ping Wang, Xing Wang, Xian Zhang, Yun-wei Shi, Lei Liu, Lingdong KongAbstract:effects on Hyperuricemia and renal dysfunction in animals. Since the decreased renal excretion of uric acid is the hallmark of Hyperuricemia, here we studied the effects of oral morin administration on renal organic ion transporters in potassium oxonate-induced hyperuricemic mice. Methods. Hyperuricemia in mice was induced by potassium oxonate. Uric acid and creatinine concentrations in urine and serum, and fractional excretion of uric acid (FEUA) were performed to evaluate renal urate handling. Changes in expression levels of renal organic ion transporters were detected by Western blotting and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) methods. Results. Morin treatment significantly increased urinary uric acid/creatinine ratio and FEUA, resulting in reduction of serum uric acid levels in hyperuricemic mice. And kidney conditions were also improved after morin treatment in this model. Protein and mRNA levels of glucose transporter 9 (mGLUT9) and urate transporter 1 (mURAT1) were significantly decreased, and of organic anion transporter 1 (mOAT1) were remarkably increased in the kidney of morin-treated hyperuricemic mice. Morin treatment also blocked down-regulations of renal organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2) in hyperuricemic mice. Conclusion. These results suggest that morin exhibits the uricosuric effects via suppressing urate reabsorption and promoting urate secretion in the kidney of hyperuricemic mice and may help to attenuate deleterious effects of Hyperuricemia with renal dysfunction
-
uricosuric and nephroprotective properties of ramulus mori ethanol extract in hyperuricemic mice
Journal of Ethnopharmacology, 2012Co-Authors: Yun-wei Shi, Cai-ping Wang, Xing Wang, Lei Liu, Yuanli Zhang, Ruwei Wang, Lingdong KongAbstract:Abstract Ethnopharmacological relevance Ramulus Mori, the branch of Morus alba , is widely used in traditional Chinese medicine prescriptions to treat gout and Hyperuricemia. Aim of this study To evaluate the uricosuric and nephroprotective effects of ethanol extract of Ramulus Mori (ERM) and explore its possible mechanisms in hyperuricemic mice. Materials and methods HPLC analysis was employed to determine the main constituents. Hyperuricemia was induced by potassium oxonate (250 mg/kg) in male mice. ERM (10, 20 and 40 mg/kg) was orally administered to hyperuricemic and normal mice for 7 days. Serum and urine levels of uric acid, creatinine and blood urea nitrogen (BUN) were measured. Simultaneously, renal mRNA and protein levels of mouse urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), organic anion transporter 1 (mOAT1) and organic cation/carnitine transporters (mOCT1/2, mOCTN1/2) were analyzed by RT-PCR and Western blotting methods. Results ERM mainly contained mulberroside A, oxyresveratrol, 4-hydroxycinnamic acid, resveratrol, 7-hydroxycumarin and morin. ERM significantly reduced serum urate levels and increased 24 h-urine urate excretion and fractional excretion of uric acid in hyperuricemic mice. It effectively restored oxonate-induced expression alteration of renal mURAT1, mGLUT9 and mOAT1, resulting in urate excretion enhancement. Moreover, ERM decreased serum creatinine and BUN levels and increased creatinine clearance, and up-regulated expression of mOCT1/2 and mOCTN1/2, contributing to kidney function improvement in this model. Conclusion These results suggest that ERM exerts the uricosuric and nephroprotective actions by the regulation of these renal organic ion transporters in hyperuricemic mice, and provide scientific support for the empirical use of Ramulus Mori.
-
protective effects of cortex fraxini coumarines against oxonate induced Hyperuricemia and renal dysfunction in mice
European Journal of Pharmacology, 2011Co-Authors: Xian Zhang, Xing Wang, Yongchang Xie, Lingdong KongAbstract:The aim of the present study was to investigate the effects of cortex fraxini coumarines esculetin, esculin, fraxetin and fraxin on renal dysfunction and expression abnormality of renal organic ion transporters in hyperuricemic animals. Mice were orally given 250 mg/kg oxonate for seven consecutive days to induce Hyperuricemia and renal dysfunction. After 1 h of oxonate induction daily, animals were orally treated with esculetin, esculin, fraxetin and fraxin at 20 and 40 mg/kg, respectively. Esculetin, esculin, fraxetin and fraxin significantly decreased serum urate, creatinine and blood urea nitrogen levels and increased urine urate and creatinine excretion in hyperuricemic mice. Esculetin and esculin up-regulated expressions of renal organic anion transporter 1 (mOAT1), organic cation and carnitine transporters (mOCT1-2 and mOCTN1-2), but failed to affect renal glucose transporter 9 (mGLUT9) and urate transporter 1 (mURAT1) in this model. Fraxetin specifically inhibited renal mURAT1, while fraxin extensively interacted with renal mGLUT9, mURAT1, mOAT1 and mOCT1 in hyperuricemic mice. Furthermore, esculetin, fraxetin and fraxin increased mABCG2 mRNA expression and decreased its protein levels in renal apical membrane in hyperuricemic mice. These results indicate that esculetin and esculin have beneficial effects on Hyperuricemia and renal dysfunction, resulting in restoration of mOAT1, mOCT1-2 and mOCTN1-2, and fraxetin and fraxin enhance urate excretion partly by inhibiting mURAT1 or mGLUT9 in kidney of hyperuricemic mice. Regulation of mABCG2 by cortex fraxini coumarines may be partly contributed to their beneficial actions. This study provides an evidence to support clinical therapeutic effects of cortex fraxini coumarines on Hyperuricemia with renal dysfunction.
-
Mulberroside a possesses potent uricosuric and nephroprotective effects in hyperuricemic mice.
Planta Medica, 2010Co-Authors: Cai-ping Wang, Xing Wang, Xian Zhang, Yemin Wang, Lingdong KongAbstract:Mulberroside A is a major stilbene glycoside of MORUS ALBA L. (Moraceae), which is effectively used for the treatment of Hyperuricemia and gout in traditional Chinese medicine. We examined whether mulberroside A had effects on renal urate underexcretion and dysfunction in oxonate-induced hyperuricemic mice and investigated the potential uricosuric and nephroprotective mechanisms involved. Mulberroside A at 10, 20, and 40 mg/kg decreased serum uric acid levels and increased urinary urate excretion and fractional excretion of uric acid in hyperuricemic mice. Simultaneously, it reduced serum levels of creatinine and urea nitrogen (10-40 mg/kg), urinary N-acetyl- β-D-glucosaminidase activity (10-40 mg/kg), β 2 -microglobulin (10-40 mg/kg) and albumin (20-40 mg/kg), and increased creatinine clearance (10-40 mg/kg) in hyperuricemic mice. Furthermore, mulberroside A downregulated mRNA and protein levels of renal glucose transporter 9 (mGLUT9) and urate transporter 1 (mURAT1), and upregulated mRNA and protein levels of renal organic anion transporter 1 (mOAT1) and organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1, and mOCTN2) in hyperuricemic mice. This is the first study demonstrating that mulberroside A exhibits uricosuric and nephroprotective effects mediated in part by cooperative attenuation of the expression alterations of renal organic ion transporters in hyperuricemic mice. These data suggest that mulberroside A may be a new drug candidate for the treatment of Hyperuricemia with renal dysfunction.
-
Morin Improves Urate Excretion and Kidney Function through Regulation of Renal Organic Ion Transporters in Hyperuricemic Mice
Journal of Pharmacy and Pharmaceutical Sciences, 2010Co-Authors: Cai-ping Wang, Xing Wang, Xian Zhang, Lingdong KongAbstract:Purpose. Morin (3,5,7,2′,4′-pentahydroxyflavone), a plant-derived flavonoid, has beneficial effects in animals with various diseases including Hyperuricemia and renal dysfunction. Since the decreased renal excretion of uric acid is the hallmark of Hyperuricemia and renal dysfunction, here we studied the effects of oral morin administration on renal organic ion transporters in oxonate-induced hyperuricemic mice. Methods. The Hyperuricemia in mice was induced by potassium oxonate. Uric acid and creatinine concentrations in urine and serum, and fractional excretion of uric acid (FEUA) were performed to evaluate urate handling. Changes in the expression levels of renal organic ion transporters were detected by Western blotting and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Results. Morin treatment significantly reduced urinary uric acid/creatinine ratio and FEUA, resulting in the reduction of serum uric acid levels in hyperuricemic mice. And kidney dysfunction was also improved after morin treatment in this model. Protein and mRNA levels of renal glucose transporter 9 (mGLUT9) and urate transporter 1 (mURAT1) were significantly decreased, and renal organic anion transporter (mOAT1) levels were remarkably increased in morin-treated hyperuricemic mice. Morin treatment also blocked down-regulation of renal organic cation and carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2) in hyperuricemic mice. Conclusion. These results suggest that morin exhibits uricosuric effect via suppressing urate reabsorption and promoting urate secretion in the kidney of hyperuricemic mice and may help to attenuate deleterious effects of Hyperuricemia with renal dysfunction.
Richard J. Johnson - One of the best experts on this subject based on the ideXlab platform.
-
Novel uromodulin mutation in familial juvenile hyperuricemic nephropathy.
American Journal of Nephrology, 2012Co-Authors: Xin Wei, Zhenhua Yang, Yunhua Liao, Richard J. Johnson, Wei R. ChenAbstract:Background: Familial juvenile hyperuricemic nephropathy (FJHN) is an autosomal dominant disorder characterized by early onset of Hyperuricemia, decreased fraction
-
clinical outcome of Hyperuricemia in iga nephropathy a retrospective cohort study and randomized controlled trial
Kidney & Blood Pressure Research, 2012Co-Authors: Y Shi, W Chen, Diana Jalal, H Mao, Q Yang, Richard J. JohnsonAbstract:Background: Hyperuricemia is an independent risk factor for renal progression in IgA nephropathy (IgAN). However, no study has evaluated the effect of allopurinol on the clinical outcome in hyperuricemic IgAN. Methods: First,a retrospective cohort study of 353 IgAN patients was conducted to explore the relationship between uric acid (UA) and the progression of renal disease over a mean period of 5 years. Then, 40 hyperuricemic IgAN patients were randomized to receive allopurinol (100–300 mg/day) or usual therapy for 6 months. The study outcomes were renal disease progression and/or blood pressure. Results: Hyperuricemia independently predicted renal survival at 1, 3, and 5 years after adjustment for different baseline estimated glomerular filtration rates. In the randomized controlled trial, allopurinol did not significantly alter renal progression or proteinuria. The antihypertensive drug dosage was reduced in 7 of 9 cases with hypertension in the allopurinol group compared to 0 of 9 cases in the control group (p Conclusion: Hyperuricemia predicts the progression of IgAN independently of baseline estimated glomerular filtration rate. Allopurinol may improve the control of blood pressure. Further studies are required to explore the effects of lowering UA on renal protection in IgAN.
-
a randomized study of allopurinol on endothelial function and estimated glomular filtration rate in asymptomatic hyperuricemic subjects with normal renal function
Clinical Journal of The American Society of Nephrology, 2011Co-Authors: Mehmet Kanbay, Bulent Huddam, Alper Azak, Yalcin Solak, Gulay Kocak Kadioglu, Ismail Kirbas, Murat Duranay, Adrian Covic, Richard J. JohnsonAbstract:Summary Background and objectives Endothelial dysfunction is an early manifestation of vascular injury and contributes to the development of atherosclerotic cardiovascular disease. Recent studies have implicated Hyperuricemia as a risk factor for cardiovascular disease. We hypothesized that lowering uric acid in subjects with asymptomatic Hyperuricemia with allopurinol might improve endothelial dysfunction, BP, estimated GFR (eGFR), and inflammatory markers. Design, setting, participants, & measurements Subjects with asymptomatic Hyperuricemia and no history of gout and 30 normouricemic control subjects were enrolled in this 4-month randomized prospective study. Thirty hyperuricemic patients received 300 mg/d allopurinol and were compared with 37 hyperuricemic patients and 30 normouricemic subjects in matched control groups. Flow-mediated dilation (FMD), eGFR, ambulatory BP monitoring, spot urine protein-creatine ratio, and highly sensitive C-reactive protein were measured at baseline and at 4 months. Results Age, gender, lipid profile, eGFR, hemoglobin, glucose, and level of proteinuria were similar in hyperuricemic subjects and controls at baseline. As expected, hyperuricemic patients had higher levels of highly sensitive C-reactive protein and lower FMD compared with normouricemic patients. Allopurinol treatment resulted in a decrease in serum uric acid, a decrease in systolic BP, an increase in FMD, and an increase in eGFR compared with baseline. No significant difference was observed in the control hyperuricemic and normouricemic groups. In a multiple regression analysis, FMD levels were independently related to uric acid both before (beta = −0.55) and after (beta = −0.40) treatment. Conclusions Treatment of Hyperuricemia with allopurinol improves endothelial dysfunction and eGFR in subjects with asymptomatic Hyperuricemia.
-
Hyperuricemia induces endothelial dysfunction
Kidney International, 2005Co-Authors: Uday M Khosla, Sergey Zharikov, Jennifer Finch, Takahiko Nakagawa, Carlos Roncal, Karina Krotova, Edward R Block, Sharma Prabhakar, Richard J. JohnsonAbstract:Hyperuricemia induces endothelial dysfunction. Background Hyperuricemia has been linked to cardiovascular and renal diseases, possibly through the generation of reactive oxygen species (ROS) and subsequent endothelial dysfunction. The enzymatic effect of xanthine oxidase is the production of ROS and uric acid. Studies have shown that inhibiting xanthine oxidase with allopurinol can reverse endothelial dysfunction. Furthermore, rat studies have shown that Hyperuricemia-induced hypertension and vascular disease is at least partially reversed by the supplementation of the nitric oxide synthase (NOS) substrate, L-arginine. Therefore, we hypothesized that uric acid induces endothelial dysfunction by inhibiting nitric oxide production. Methods Hyperuricemia was induced in male Sprague-Dawley rats with an uricase inhibitor, oxonic acid, by gavage; control rats received vehicle. Allopurinol was placed in drinking water to block Hyperuricemia. Rats were randomly divided into four groups: ( 1 ) control, (2) allopurinol only, ( 3 ) oxonic acid only, and ( 4 ) oxonic acid + allopurinol. Rats were sacrificed at 1 and 7 days, and their serum analyzed for serum uric acid and nitrites/nitrates concentrations. The effect of uric acid on nitric oxide production was also determined in bovine aortic endothelial cells. Results Oxonic acid induced mild Hyperuricemia at both 1 and 7 days ( P P X ) were reduced in hyperuricemic rats at both 1 and 7 days ( P X at 1 day and completely at 7 days ( P X ( R 2 = 0.56) and a trend toward higher systolic blood pressure in hyperuricemic rats ( P = NS). Uric acid was also found to inhibit both basal and vascular endothelial growth factor (VEGF)-induced nitric oxide production in bovine aortic endothelial cells. Conclusion Hyperuricemic rats have a decrease in serum nitric oxide which is reversed by lowering uric acid levels. Soluble uric acid also impairs nitric oxide generation in cultured endothelial cells. Thus, Hyperuricemia induces endothelial dysfunction; this may provide insight into a pathogenic mechanism by which uric acid may induce hypertension and vascular disease.
-
Hemodynamics of Hyperuricemia.
Seminars in nephrology, 2005Co-Authors: Laura G. Sánchez-lozada, Richard J. Johnson, Edilia Tapia, Bernardo Rodriguez-iturbe, Jaime Herrera-acostaAbstract:Prolonged Hyperuricemia is associated with the development of hypertension, renal arteriolosclerosis, glomerulosclerosis, and tubulointerstitial injury. It confers a greater risk than proteinuria for developing chronic renal disease and is associated with the development of hypertension. Mild chronic Hyperuricemia without intrarenal crystal deposition was induced in rats by inhibiting uricase with oxonic acid. Hyperuricemic rats developed hypertension, afferent arteriolar thickening, and mild renal interstitial fibrosis. Additionally, Hyperuricemia accelerated renal damage and vascular disease in rats undergoing renal ablation. To better understand the role of Hyperuricemia in the kidney, micropuncture studies were performed. Hyperuricemia resulted in renal cortical vasoconstriction (single nephron glomerular filtration rate (SNGFR) ↓ 35%, P P P
Atsushi Fukatsu - One of the best experts on this subject based on the ideXlab platform.
-
Restored expression and activity of organic ion transporters rOAT1, rOAT3 and rOCT2 after Hyperuricemia in the rat kidney
Biochemical Pharmacology, 2005Co-Authors: Yasushi Habu, Ikuko Yano, Masahiro Okuda, Atsushi FukatsuAbstract:Abstract We previously reported that in hyperuricemic rats, renal impairment occurred and organic ion transport activity decreased, accompanied with a specific decrease in the expression of rat organic anion transporters, rOAT1 and rOAT3, and organic cation transporter, rOCT2. In the present study, we investigated the reversibility of the organic ion transport activity and expression of organic ion transporters (slc22a) during recovery from Hyperuricemia. Hyperuricemia was induced by the administration of a chow containing uric acid and oxonic acid, an inhibitor of uric acid metabolism. Four days after discontinuance of the chow, the plasma uric acid concentration returned to the normal level, and renal functions such as creatinine clearance and BUN levels were restored, although the recovery of tubulointerstitial injury was varied in sites of the kidney. Basolateral uptake of p -aminohippurate (PAH) and tetraethylammonium (TEA), and both protein and mRNA levels of rOAT1, rOAT3 and rOCT2 in the kidney gradually improved during 14 days of recovery from Hyperuricemia. Basolateral PAH transport showed a higher correlation with the protein level of rOAT1 ( r 2 = 0.80) than rOAT3 ( r 2 = 0.34), whereas basolateral TEA transport showed a strong correlation with rOCT2 protein ( r 2 = 0.91). The plasma testosterone concentration, which is a dominant factor in the regulation of rOCT2, was gradually restored during the recovery from Hyperuricemia, but the correlation between the plasma testosterone level and rOCT2 protein expression in the kidney was not significant. These results suggest that the regulation of organic ion transporters, rOAT1, rOAT3 and rOCT2, by Hyperuricemia is reversible, and the organic ion transport activity restores according to the expression levels of these transporters.
-
Decreased activity of basolateral organic ion transports in hyperuricemic rat kidney: roles of organic ion transporters, rOAT1, rOAT3 and rOCT2.
Biochemical Pharmacology, 2003Co-Authors: Yasushi Habu, Hideyuki Saito, Ikuko Yano, Masahiro Okuda, Ayako Takeuchi, Atsushi FukatsuAbstract:Abstract We investigated organic anion and cation transport activity and the expression of several organic ion transporters in hyperuricemic rat kidney. Feeding oxonic acid, an inhibitor of uric acid metabolism, and uric acid for 10 days significantly increased plasma uric acid level. Plasma creatinine and blood urea nitrogen concentrations also increased in hyperuricemic rats, indicating impaired renal function. The accumulation of organic anions, p-aminohippurate (PAH) and methotrexate, and cations, tetraethylammonium (TEA) and cimetidine, into renal slices was markedly decreased, suggesting decreased transport activity for organic anions and cations at the basolateral membrane in the kidney. The expression levels of basolateral organic anion transporters rOAT1 and rOAT3, and organic cation transporter, rOCT2, significantly decreased in hyperuricemic rat kidney as assessed by mRNA and protein levels. In contrast, the expression of rOCT1 was unaltered by Hyperuricemia at both mRNA and protein levels. Moreover, the mRNA expression of kidney-specific organic anion transporters, OAT-K1 and OAT-K2, and organic anion transporting polypeptide (oatp) 1, which localize at the brush-border membrane in the kidney, was unchanged in hyperuricemic rats. In conclusion, we showed decreased basolateral organic anion and cation transport activity, accompanied by a specific decrease in rOAT1, rOAT3 and rOCT2 expression in hyperuricemic rat kidney. These phenomena partly contribute to the changed renal disposition of organic anions and cations in Hyperuricemia.
Jun Zhang - One of the best experts on this subject based on the ideXlab platform.
-
pallidifloside d from smilax riparia enhanced allopurinol effects in Hyperuricemia mice
Fitoterapia, 2015Co-Authors: Piyong Hou, Jun Zhang, Shuqing Wang, Samantha Anderson, Yanwen ZhangAbstract:Pallidifloside D, a saponin glycoside constituent from the total saponins of Smilax riparia, had been proved to be effective in hyperuricemic control. Allopurinol is a commonly used medication to treat Hyperuricemia and its complications. In this study, we evaluated whether Pallidifloside D could enhance allopurinol’s effects by decreasing the serum uric acid level in a hyperuricemic mouse model induced by potassium oxonate. We found that, compared with allopurinol alone, the combination of allopurinol and Pallidifloside D significantly decreased the serum uric acid level and increased the urine uric acid level (both P<0.05), leading to the normalized serum and urine uric acid concentrations. Data on serum, urine creatinine and BUN supported these observations. Our results showed that the synergistic effects of allopurinol combined with Pallidifloside D was linked to the inhibition of both serum and hepatic xanthine oxidase (XOD), the down-regulation of renal mURAT1 and mGLUT9, and the up-regulation of mOAT1. Our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions.
-
anti Hyperuricemia effects of allopurinol are improved by smilax riparia a traditional chinese herbal medicine
Journal of Ethnopharmacology, 2015Co-Authors: Chongzhi Wang, Jun Zhang, Shuqing Wang, Yanwen Zhang, Samantha Anderson, Chunsu YuanAbstract:Abstract Ethnopharmacological relevance The roots and rhizomes of Smilax riparia are called “Niu-Wei-Cai” in traditional Chinese medicine (TCM). This botanical has been used in treating the symptoms of gout and other hyperuricemic-related conditions in TCM. Allopurinol is a commonly used medication to treat Hyperuricemia and its complications. In this study, we evaluated whether Smilax riparia could enhance allopurinol׳s effects by decreasing the serum uric acid level in a hyperuricemic mouse model induced by potassium oxonate. Materials and methods We examined the effects of allopurinol (5 mg/kg) administration alone or in combination with Smilax riparia saponins (SRS, 500 mg/kg) on the serum uric acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels in a hyperuricemic mouse model. The effects of allopurinol alone or those of allopurinol plus SRS on the XOD activities were measured. Western blot analysis was used to measure the levels of mURAT1, mGLUT9 and mOTA1 in the mice. Results Compared with allopurinol alone, the combination of allopurinol and SRS significantly decreased the serum uric acid level and increased the urine uric acid level (both P Conclusion The anti-Hyperuricemia effects of allopurinol are improved by Smilax riparia co-administration. The results were supported by the measurement of uric acid, creatinine, BUN, XOD, mURAT1, mGLUT9 and mOAT1. Our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions.
-
pallidifloside d a saponin glycoside constituent from smilax riparia resist to Hyperuricemia based on urat1 and glut9 in hyperuricemic mice
Journal of Ethnopharmacology, 2014Co-Authors: Jinlan Ruan, Jun Zhang, Shuqing Wang, Yanwen ZhangAbstract:Abstract Ethnopharmacological relevance The roots and rhizomes of Smilax riparia (SR), called “Niu-Wei-Cai” in traditional Chinese medicine (TCM), are believed to be effective in treating Hyperuricemia and gout symptoms. This study was designed to isolate a saponin glycoside named pallidifloside D from the total saponins of Smilax riparia and to examine its effect in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. Materials and methods We examined the effects of pallidifloside D treated with 5, 10 and 20 mg/kg on serum uric acid levels (SUA), Serum creatinine (SCr) and blood urea nitrogen (BUN) levels in a hyperuricemic mouse. A colorimetric method was used to evaluate the effects of pallidifloside D on the XOD activities, and Western Blotting analysis were carried out to observe protein levels of mURAT1, mGLUT9 and mOTA1 in hyperuricemic mice after treatment with pallidifloside D. Results The levels of serum uric acid levels (SUA) were suppressed significantly with dose-dependence by pallidifloside D treated with 5, 10 and 20 mg/kg (p Conclusion These results suggest that pallidifloside D possesses a potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1 and GLUT9, which contribute to the enhancement of uric acid excretion and attenuate Hyperuricemia-induced renal dysfunction.
-
riparoside b and timosaponin j two steroidal glycosides from smilax riparia resist to Hyperuricemia based on urat1 in hyperuricemic mice
Phytomedicine, 2014Co-Authors: Jun Zhang, Shuqing Wang, Victor C Yang, Samantha Anderson, Yanwen ZhangAbstract:The roots and rhizomes of Smilax riparia (SR), called “Niu-Wei-Cai” in traditional Chinese medicine (TCM), are believed to be effective in treating gout symptoms. However, it is not clear if the active constituents and uricosuric mechanisms of S. riparia support its therapeutic activities. In this study, we isolated two steroidal glycosides named riparoside B and timosaponin J from the total saponins of S. riparia. We then examined if these two compounds were effective in reducing serum uric acid levels in a hyperuricemic mouse model induced by potassium oxonate. We found that the two steroidal glycosides possess potent uricosuric effect in hyperuricemic mice through decreasing renal mURAT1 mainly and inhibiting XOD activity in a certain extent, which contribute to the enhancement of uric acid excretion and attenuate Hyperuricemia-induced renal dysfunction. Riparoside B and timosaponin J may have a clinical utility in treating gout and other medical conditions caused by Hyperuricemia.