Caiping Wang

The dual actions of Sanmiao wan as a hypouricemic agent: down-regulation of hepatic XOD and renal mURAT1 in hyperuricemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE Sanmiao wan (SMW) is widely used for the treatment of gout and hyperuricemia in traditional Chinese medicine. AIM OF THE STUDY The aim of the present study was to investigate the hypouricemic effects of SMW and its possible mechanism in potassium oxonate-induced hyperuricemic mice. MATERIALS AND METHODS SMW at 489, 978 and 1956 mg/kg was orally administered to hyperuricemic and normal mice, and standard drug allopurinol (2.5mg/kg) was served as a positive control. The effects of SMW on serum, urine and liver levels of uric acid, serum levels of creatinine, and activity of hepatic xanthine oxidase (XOD) were measured in mice. Moreover, the effects of SMW on the mRNA and protein levels of hepatic XOD and renal urate transporter 1 (mURAT1) in mice were analyzed by semi-quantitative RT-PCR and Western blotting methods, respectively. RESULTS SMW significantly reduced uric acid levels in serum and liver, inhibited hepatic XOD activity, mRNA and protein levels in hyperuricemic mice. Furthermore, SMW could effectively down-regulate renal mURAT1 mRNA and protein levels of hyperuricemic mice. And it reversed oxonate-induced elevation in serum creatinine levels of mice. However, SMW did not show any effects in normal mice. CONCLUSION These findings suggested that SMW produced dual hypouricemic actions by suppressing hepatic XOD to reduce uric acid production and down-regulating renal mURAT1 to decrease urate reabsorption and enhance urate excretion in hyperuricemic mice.

Mulberroside A Possesses Potent Uricosuric and Nephroprotective Effects in Hyperuricemic Mice

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), β₂-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.

Uricosuric and nephroprotective properties of Ramulus Mori ethanol extract in hyperuricemic mice

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 24h-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.

Combined administration of the mixture of honokiol and magnolol and ginger oil evokes antidepressant-like synergism in rats

Magnolia bark combined with ginger rhizome is a common drug pair in traditional Chinese prescriptions for the treatment of depression. In the present study, we examined antidepressant-like effects of the mixture of honokiol and magnolol (HMM) from magnolia bark and essential oil from ginger rhizome (OGR) alone and in combination in chronic unpredictable mild stress (CUMS) of rats. Behavioral (sucrose intake, immobility time of forced swimming test) and biochemical parameters [serotonin (5-HT) in prefrontal cortex, hippocampus, and striatum, gastric mucosa cholecystokinin (CCK) and serum gastrin (GAS) levels] were simultaneously examined in the CUMS rats. 20 mg/kg HMM alone, but not OGR, significantly increased sucrose intake and reduced immobility time in the CUMS rats. Moreover, 20 mg/kg HMM and 14 mg/kg OGR in combination exhibited significant synergistic effects on sucrose intake increase and immobility time reduction in the CUMS rats. HMM elevated 5-HT levels in various brain regions, and OGR reduced gastric mucosa CCK and serum GAS levels in the CUMS rats. These results suggested that the synergistic antidepressant-like effects of compatibility of HMM with OGR might be mediated simultaneously by regulation of the serotonergic and gastroenteric system functions. These findings also provided a pharmacological basis for the clinical application of this drug pair of magnolia bark and ginger rhizome in traditional Chinese medicine.

Morin Improves Urate Excretion and Kidney Function through Regulation of Renal Organic Ion Transporters in Hyperuricemic Mice

PURPOSE Morin (2′,3,4′,5,7-pentahydroxyflavone), a plant-derived flavonoid, has beneficial 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.