Hypouricemic Effects of Extracts from Urtica hyperborea Jacq. ex Wedd. in Hyperuricemia Mice through XOD, URAT1, and OAT1

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.

Anti-Hyperuricemic Effects of Astaxanthin by Regulating Xanthine Oxidase, Adenosine Deaminase and Urate Transporters in Rats

“…The high levels of fructose metabolism in liver increased the enzymatic activities of XOD and ADA, which are the pathogenic factors for HUA [35,36]. Whereas, in the ALL group, the allopurinol inhibited the enzymatic activities of XOD and ADA in liver (Figure 2), which was consistent with the previous studies [37,38]. As compared to the model group, the enzymatic activities of XOD and ADA in the AST groups decreased significantly (Figure 2).…”

Bioactive Compounds from Plant-Based Functional Foods: A Promising Choice for the Prevention and Management of Hyperuricemia

“…XOD catalyzes the oxidation of hypoxanthine to xanthine and xanthine to UA [16]. ADA plays a key role in indirectly catalyzing the formation of UA [17]. Thus, inhibiting UA synthesis through XOD and ADA inhibition can be considered a therapeutic target to reduce the level of UA in the body.…”

“…In addition, ADA catalyzes the conversion of adenosine to inosine, which in turn is catalyzed to hypoxanthine and xanthine. Therefore, ADA plays a key role in indirectly catalyzing the formation of UA [17]. The catalytic process for UA production is presented in Figure 1.…”

Apostichopus japonicus Oligopeptide Induced Heterogeneity in the Gastrointestinal Tract Microbiota and Alleviated Hyperuricemia in a Microbiota‐Dependent Manner

“…[ 2 ] Uric acid is mainly produced in the liver and is metabolized via cooperative excretion by multiple transporters in the kidney. [ 3 ] Therefore, compounds that inhibit uric acid synthesis and promote excretion have been widely used to reduce uric acid levels in patients with hyperuricemia. However, due to the potential adverse effects of these clinical drugs, [ 4 ] it is necessary to discover alternatives to medication for hyperuricemia treatment.…”