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.