Effect of Eurycoma longifolia Stem Extract on Uric Acid Excretion in Hyperuricemia Mice
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,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.01464/full |
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| author | Ruixia Bao Mengyang Liu Dan Wang Shaoshi Wen Haiyang Yu Yi Zhong Zheng Li Yi Zhang Tao Wang |
| author_facet | Ruixia Bao Mengyang Liu Dan Wang Shaoshi Wen Haiyang Yu Yi Zhong Zheng Li Yi Zhang Tao Wang |
| author_sort | Ruixia Bao |
| collection | DOAJ |
| description | 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 down-regulated, 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.Conclusion: Our findings revealed that EL significantly reduced blood uric acid levels, prevented pathological changes of kidney in PO induced hyperuricemia animal model, and improved renal urate transports. We partly clarified the mechanism was related to suppressing effect of URAT1 by quassinoid in EL. This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion. |
| first_indexed | 2024-12-19T09:03:35Z |
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| id | doaj.art-d502b4bc6aa54502b6b1d6ba30afdea6 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T09:03:35Z |
| publishDate | 2019-12-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-d502b4bc6aa54502b6b1d6ba30afdea62022-12-21T20:28:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-12-011010.3389/fphar.2019.01464483331Effect of Eurycoma longifolia Stem Extract on Uric Acid Excretion in Hyperuricemia MiceRuixia Bao0Mengyang Liu1Dan Wang2Shaoshi Wen3Haiyang Yu4Yi Zhong5Zheng Li6Yi Zhang7Tao Wang8Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaTianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaKey Laboratory of Pharmacology of Traditional Chinese Medical Formulae (Tianjin University of Traditional Chinese Medicine), Ministry of Education, Tianjin, ChinaTianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaKey Laboratory of Pharmacology of Traditional Chinese Medical Formulae (Tianjin University of Traditional Chinese Medicine), Ministry of Education, Tianjin, ChinaHerb Research Centre, Global Education Network Sdn.Bhd., Puchong, MalaysiaTianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaTianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaInstitute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaBackground: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 down-regulated, 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.Conclusion: Our findings revealed that EL significantly reduced blood uric acid levels, prevented pathological changes of kidney in PO induced hyperuricemia animal model, and improved renal urate transports. We partly clarified the mechanism was related to suppressing effect of URAT1 by quassinoid in EL. This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion.https://www.frontiersin.org/article/10.3389/fphar.2019.01464/fullEurycoma longifoliaeurycomanolhyperuricemiauric acid excretionurate reabsorption transporter |
| spellingShingle | Ruixia Bao Mengyang Liu Dan Wang Shaoshi Wen Haiyang Yu Yi Zhong Zheng Li Yi Zhang Tao Wang Effect of Eurycoma longifolia Stem Extract on Uric Acid Excretion in Hyperuricemia Mice Frontiers in Pharmacology Eurycoma longifolia eurycomanol hyperuricemia uric acid excretion urate reabsorption transporter |
| title | Effect of Eurycoma longifolia Stem Extract on Uric Acid Excretion in Hyperuricemia Mice |
| title_full | Effect of Eurycoma longifolia Stem Extract on Uric Acid Excretion in Hyperuricemia Mice |
| title_fullStr | Effect of Eurycoma longifolia Stem Extract on Uric Acid Excretion in Hyperuricemia Mice |
| title_full_unstemmed | Effect of Eurycoma longifolia Stem Extract on Uric Acid Excretion in Hyperuricemia Mice |
| title_short | Effect of Eurycoma longifolia Stem Extract on Uric Acid Excretion in Hyperuricemia Mice |
| title_sort | effect of eurycoma longifolia stem extract on uric acid excretion in hyperuricemia mice |
| topic | Eurycoma longifolia eurycomanol hyperuricemia uric acid excretion urate reabsorption transporter |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.01464/full |
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