Eurycomanol alleviates hyperuricemia by promoting uric acid excretion and reducing purine synthesis

高尿酸血症 化学 尿酸 排泄 嘌呤 黄嘌呤氧化酶 药理学 Abcg2型 痛风 生物化学 内科学 医学 运输机 ATP结合盒运输机 基因
作者
Ruixia Bao,Qian Chen,Zheng Li,Dan Wang,Yuzheng Wu,Mengyang Li,Yi Zhang,Tao Wang
出处
期刊:Phytomedicine [Elsevier]
卷期号:96: 153850-153850 被引量:14
标识
DOI:10.1016/j.phymed.2021.153850
摘要

An elevated level of blood uric acid (UA) leads to serious damages to human health. In clinic, xanthine oxidase inhibitor is commonly used to reduce uric acid production. However, UA excretion promotion drug is rare. Our previous study demonstrated that the 70% ethanolic extract of stem of Eurycoma longifolia could effectively increase UA excretion and decrease blood level of UA in hyperuricemia animal model. In this paper, we tried to find active substance on UA regulation from E. longifolia.The constituents of stem from E. longifolia were isolated and analyzed by chemical and spectral methods. Ultra Performance Liquid Chromatography was applied to measure the concentrations of UA in serum and urine. H&E staining was used to characterize renal histopathological changes. The protein and mRNA expressions of UA transporters were measured by western blot and quantitative real-time PCR analysis.Ten kinds of quassinoids were isolated from stem of E. longifolia, and the structures were identified. Pharmacological research revealed the major component, eurycomanol (5-20 mg/kg, p.o.) significantly decreased serum UA level and increased 24 h clearance of uric acid in potassium oxonate and adenine induced hyperuricemic mice. Eurycomanol ameliorated UA induced kidney histological injury, inhibited hepatic purine synthesis through decreasing phosphoribosyl pyrophosphate synthetase, promoted UA excretion by modulation of renal and intestinal urate transporters, such as GLUT9, ABCG2, OAT1, and NPT1.The results showed eurycomanol from E. longifolia can promote UA excretion through kidney and intestine, decrease hepatic purine synthesis and further keep UA homeostasis, suggesting that eurycomanol has the potential to be developed into a novel drug for the treatment of under-excretion type hyperuricemia.
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