Effect of Eurycoma longifolia Stem Extract on Uric Acid Excretion in Hyperuricemia Mice

Abstract

Background: Eurycoma longifolia is a tropical medicinal plant belonging to Simaroubaceae distributed in South East Asia. The stems are traditionally used for the treatment of sexual insufficiency, fever, hypertension, and malaria. Furthermore, it has antidiabetic and anticancer activities. Recently, it has been reported to reduce uric acid, but the mechanism is unclear. Hypothesis/Purpose: The aim of this study is to explore the effect and mechanism of E. longifolia stem 70% ethanol extract (EL) and its active compounds on uric acid excretion. Study Design and Methods: Potassium oxonate (PO) induced hyperuricemia rats model and adenine-PO induced hyperuricemia mice model were used to evaluate the effects of EL. Ultraperformance liquid chromatography was used to determine the levels of plasma or serum uric acid and creatinine. Hematoxylin-eosin staining was applied to observe kidney pathological changes, and western blot was applied to detect protein expression levels of uric acid transporters. Effects of constituents on urate uptake were tested in hURAT1-expressing HEK293T cells. Results: EL significantly reduced serum and plasma uric acid levels at dosages of 100, 200, and 400 mg/kg in hyperuricemia rats and mice, increased the clearance rate of uric acid and creatinine, and improved the renal pathological injury. The protein expression levels of urate reabsorption transporter 1 (URAT1) and glucose transporter 9 were downregulated, while sodium-dependent phosphate transporter 1 and ATP-binding cassette transporter G2 were up-regulated in the kidney after EL treatment. The quassinoids isolated from EL showed inhibitory effects on urate uptake in hURAT1-expressing HEK293T cells, and the effect of eurycomanol was further confirmed in vivo.

Antihyperuricemic Effect of Dendropanax morbifera Leaf Extract in Rodent Models

“…Although ALP belonging to XO inhibitors has been mainly used to treat Evidence-Based Complementary and Alternative Medicine hyperuricemia, this drug has been associated with severe cutaneous adverse reactions [33]. erefore, many previous studies have been conducted to develop safe therapeutic agents using natural products for hyperuricemia without side effects [14,19,30]. is study showed the antioxidant, XOD-inhibitory, and antihyperuricemic activities of DMLEs and determined active components.…”

“…erefore, more effective therapeutic agents for hyperuricemia with no adverse effects are needed. In previous studies, new therapeutic methods using herbs were offered to overcome these limitations of drugs for hyperuricemia [19].…”

The Time-Feature of Uric Acid Excretion in Hyperuricemia Mice Induced by Potassium Oxonate and Adenine

“…The method of protein samples preparation was reported in literature [ 29 ]. SDS-polyacrylamide gel (SDS-PAGE) electrophoresis was used to isolate protein and then transferred to PVDF membrane (Merck Millipore, Bedford, MA, USA).…”

“…According to the literature, potassium oxonate (PO) (an uricase inhibitor) with or without high purine food is usually used as hyperuricemia inducer in rats/mice, but the experimental protocols are different. For example, the duration of modeling was 7 [ 26 ] or 14 days [ 27 ], PO was orally [ 28 ] or intraperitoneally injected [ 26 ], PO dose was 200 [ 29 ], 250 [ 30 ] or 300 mg/kg [ 31 ], etc. The administration time is not uniform, resulting in a large difference between the data by different research groups, with some opposite results.…”

A review of the phytochemical compounds and pharmacological activities of Eurycoma longifolia

“…Quassinoids in E. longifolia hadhuman urate transporter 1 (URAT1) inhibition activity by reducing blood uric acid levels in induced hyperuricemia animal model (Bao et al, 2019). Study by Liu et al (2019) presented that E. longifolia reduced ankle swelling caused by gout in low and medium doses which indicated that E. longifolia has anti-gout effect.…”