Emodinol, 1β,3β,23-trihydroxyolean-12-en-28-acid, as the main active ingredient firstly extracted from the rhizomes of Elaeagus pungens by our research group, has been demonstrated to exhibit uricosuric activity by our previous study. The aim of this study was to evaluate the uricosuric and nephroprotective effects of
emodinol and explore its possible mechanisms in
potassium oxonate-induced hyperuricemic mice with renal dysfunction. Mice were orally administrated 250 mg/kg of
potassium oxonate once daily for 7 consecutive days to induce
hyperuricemia with renal dysfunction.
Emodinol was given at doses of 25, 50, and 100 mg/kg on the same day 1 h after oxonate treatment, and
allopurinol (10 mg/kg) was given as a positive control. After 1 week, serum
uric acid, serum
creatinine, urine
uric acid, urine
creatinine, blood
urea nitrogen, and hepatic
xanthine oxidase activity were determined. The
mRNA and
protein levels of
urate transporter 1,
glucose transporter 9,
ATP-binding cassette subfamily G member 2,
organic anion transporter 1,
oncoprotein-induced transcript 3, and organic
cation/
carnitine transporters in the kidney were detected by real-time polymerase chain reaction and Western blot analysis. In addition, urinary and renal
Tamm-Horsfall glycoprotein concentrations were examined by ELISA assays.
Emodinol significantly reduced serum
urate levels, increased urinary
urate levels and fractional excretion of
uric acid, and inhibited hepatic
xanthine oxidase activity in hyperuricemic mice. Moreover,
potassium oxonate administration led to dys expressions of renal
urate transporter 1,
glucose transporter 9,
ATP-binding cassette subfamily G member 2,
organic anion transporter 1, and
oncoprotein-induced transcript 3 as well as alternations of
uromodulin concentrations, which could be reversed by
emodinol. On the other hand, treatment of
emodinol caused upregulated expressions of organic
cation/
carnitine transporters, resulting in an improvement of renal function characterized by decreased serum
creatinine and blood
urea nitrogen levels.
Emodinol exhibited hypouricemic and nephroprotective actions by inhibiting
xanthine oxidase activity and regulating renal ion transporters and
oncoprotein-induced transcript 3, which may be a potential therapeutic agent in
hyperuricemia and renal dysfunction.