Mulberroside A Possesses Potent Uricosuric and Nephroprotective Effects in Hyperuricemic Mice

Abstract

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.

Key words

mulberroside A - hyperuricemia - uricosuric - nephroprotective - organic anion transporters - organic cation/carnitine transporters - Morus alba L. - Moraceae

References

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