Molecular mechanistic insight into the anti-hyperuricemic effect of Eucommia ulmoides in mice and rats

Abstract

Context: Eucommia ulmoides Oliver (Eucommiaceae) has various medicinal properties. Our previous studies revealed that Eucommia ulmoides has a protective effect on hyperuricaemia. Objective: This study investigates the effect of Eucommia ulmoides cortex ethanol extract (EU) on hyperuricaemia and explores the underlying mechanism in Kunming mice and Sprague–Dawley rats. Material and methods: Sixty mice and sixty rats were divided into normal control, hyperuricaemia, allopurinol (10 mg/kg) and three EU groups. The EU groups received intragastric EU at 80, 160, 320 mg/kg in mice and 100, 200, 400 mg/kg in rats for 7 days. Serum uric acid (SUA) was measured using a kit. mRNA and proteins were quantified by RT-qPCR and immunohistochemical assays (IHC), respectively. Results: The Maximal Tolerable Dose (MTD) of EU administered intragastrically was 18 g/kg in mice. The intermediate (160 mg/kg) and high (320 mg/kg) EU treatment significantly reduced (p < 0.05) SUA levels to 130.16 μmol/L and 109.29 μmol/L, respectively, and markedly elevated the mRNA expression of organic anion transporters 1 (OAT1) and organic anion transporters 3 (OAT3), while significantly deceasing the mRNA levels of glucose transporter 9 (GLUT9) and uric acid transporter 1 (URAT1) in the mouse kidney (p < 0.05). In hyperuricemic rats, high EU (400 mg/kg) significantly reduced SUA levels to 253.85 μmol/L, and increased OAT1 and OAT3 levels, but decreased URAT1 and GLUT9, compared to the hyperuricaemia group (p < 0.05). Discussion and conclusions: This study demonstrated the potential hyperuricaemia ameliorating effect of EU. Specific active ingredients in EU should be evaluated. These results are valuable for the development of antihyperuritic agents from EU.

Keywords

• organic anion transporter 1
• organic anion transporter 3
• glucose transporter 9
• uric acid transporter 1