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Eurycoma longifolia jack leaf extract alleviates hyperuricemia by regulating renal urate transporters
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DOI   10.11656/j.issn.1673-9043.2026.07.09
Key Words   Eurycoma longifolia jack leaf extract;hyperuricemia;urate transporter;renal excretion
Author NameAffiliationE-mail
LI Siyi Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
PAN Jujie Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
WEN Shaoshi Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
BAO Ruixia Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
CHE Ziyu Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
WANG Dan Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China Email:wangdan0048@tjutcm.edu.cn 
WANG Tao Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China wangtao@tjutcm.edu.cn 
Abstract
    [Objective] To investigate the therapeutic efficacy and underlying mechanisms of Eurycoma longifolia jack leaf extract(ELL)in regulating hyperuricemia. [Methods] A mouse model of hyperuricemia was established via continuous 3-week co-administration of potassium oxonate and adenine. Serum uric acid(SUA)and creatinine levels were monitored weekly. Mice were placed in metabolic cages 24 h before sacrifice to collect urine for uric acid quantification and calculation of uric acid clearance(Cur). Renal histopathology was assessed by HE staining. RT-PCR and Western blot were employed to analyze the expression of urate transporter-related genes and proteins in kidney tissues. [Results] Progressive hyperuricemia led to decreased body weight,reduced food intake,and increased water consumption compared with normal controls. ELL at a dose of more than 200 mg/kg restored weight gain. After 1 week of modeling,SUA levels surged,accompanied by increased urine volume but decreased uric acid excretion. Cur declined significantly over time. ELL treatment markedly reduced SUA and serum creatinine while elevating Cur and creatinine clearance rate(Ccr). HE staining revealed that ELL alleviated renal pathological damage and improved kidney function. Molecular analyses demonstrated that ELL downregulated renal URAT1 (urate-anion transporter 1)and GLUT9(glucose transporter 9)expression while upregulating OAT1(organic anion transporter 1),NPT1(Na-dependent phosphate cotransporter 1),and ABCG2(ATP-binding cassette superfamily G member 2). [Conclusion] ELL lowered SUA levels in hyperuricemia mice by enhancing Cur and Ccr and protected renal tissue. The mechanism involved dual modulation of urate transporters:inhibiting reabsorption via downregulation of URAT1/GLUT9 and promoting excretion via upregulation of NPT1/OAT1/ABCG2.

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