Abstract
Urtica L. has been long used for gout in traditional Tibetan medicine and is closely related to the effect of reducing uric acid. This study aimed to investigate the effect of Urtica hyperborea Jacq. ex Wedd. (UW) on lowering uric acid and its mechanism by using HK2 cells and hyperuricemia mouse model. Petroleum ether extract (UWP), ethyl acetate extract (UWE), n-butanol extract (UWB), and alcohol-soluble extract (UWA) from UW were prepared, and HK2 cells were treated with various parts extracts to observe the expression of uric acid transporter at 25, 50, and 100 μg/mL for 24 h. Moreover, hyperuricemia mice were administered orally various parts extracts at 0.78 and 2.34 g/kg (crude drug dose converted by extraction rate) to observe the change of hepatic XOD, serum ADA, renal function, and uric acid transporter. In vitro experiments showed that UWA can remarkably elevate OAT1 expression and decrease URAT1 expression in HK2 cells. In vivo experiments showed that UWP, UWE, UWB, and UWA showed remarkable activity in reducing uric acid, rendering a substantial decline in the SUA level in hyperuricemia mice. Compared with the hyperuricemia and allopurinol groups, UWB and UWA had significant protective effects on renal injury. At the same time, UWA can significantly reduce the activity of XOD and ADA, reduce the expression of URAT1, and increase the expression of OAT1. These results indicated that UWA had an outstanding uric acid lowering effect and did not affect renal function. This may be related to increased uric acid excretion and decreased uric acid production, mediated by renal OAT1, URAT1, liver XOD, and serum ADA. UWA may be a potential drug against hyperuricemia.
Highlights
Hyperuricemia is caused by excess uric acid in the blood due to increased production of uric acid and/or impaired renal urate excretion, which is common and extremely painful inflammatory arthritis [1, 2]
At 100 μg/mL, different extracts from UW significantly reduced cell survival rate. erefore, 25 μg/mL and 50 μg/ mL were used to study the effects of different extracts from UW on the uric acid transporter in HK2 cells
SUA level in the hyperuricemia model group was significantly increased compared with the control group, indicating that the modeling was successful
Summary
Hyperuricemia is caused by excess uric acid in the blood due to increased production of uric acid and/or impaired renal urate excretion, which is common and extremely painful inflammatory arthritis [1, 2]. It is an independent risk factor for coronary heart disease, hypertension, diabetes, and other diseases [3]. There are many drugs used in clinical treatment for lowering uric acid, but there are many side effects, such as allopurinol, mainly headaches, allergies, rashes, elevated aminotransferase, nephritis, and other adverse reactions, contraindication for patients with renal dysfunction. Some research has been carried out to find active ingredients of uric acid lowering from traditional Chinese medicine [5, 6]
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