Hypouricemic Actions of the Pericarp of Mangosteen in Vitro and in Vivo

Hypouricemic Actions of the Pericarp of Mangosteen in Vitro and in Vivo
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山竹果皮的体外和体内降尿酸作用

DOI:
10.1021/acs.jnatprod.2c00531
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发表时间:
2023
影响因子:
5.1
通讯作者:
Ling Li
Ling Li
中科院分区:
生物学2区
文献类型:
--
作者:
Yanfen Niu;Qiang Li;CaixiaTu;Na Li;Lihui Gao;Hua Lin;Zhenyu Wang;Zhihong Zhou;Ling Li

文献摘要

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高尿酸血症是尿酸产生过多和/或排泄不足的结果,并且是痛风、高血压和糖尿病的众所周知的危险因素。然而,临床上可用于治疗高尿酸血症的药物有限。最近,为了从植物和食物中发现新的降尿酸剂,进行了大量的研究。我们发现山竹果果皮的萃取物可降低尿酸盐。生物活性导向研究表明,α-倒捻子素为主要成分。本文首次报道了α-倒捻子素的降尿酸作用及其机制。α-倒捻子素剂量依赖性和时间依赖性地降低高尿酸血症小鼠的血清尿酸水平,显著增加高尿酸血症大鼠的尿酸清除率,表现出促进肾脏中尿酸排泄。进一步的证据表明,α-mangostin显著降低了肾脏中GLUT 9的蛋白水平。未观察到URAT 1表达的变化。此外,α-倒捻子素在体外和体内均不抑制黄嘌呤氧化还原酶和尿酸酶的活性。综上所述,这些发现表明α-mangostin有潜力被开发为一种新的抗高尿酸血症药物,促进尿酸排泄。
Hyperuricemia is the result of overproduction and/or underexcretion of uric acid, and it is a well-known risk factor for gout, hypertension, and diabetes. However, available drugs for hyperuricemia in the clinic are limited. Recently, a lot of research has been conducted in order to discover new uric acid-lowering agents from plants and foods. We found that the extracts from the pericarp of mangosteen reduced urate. Bioactivity-guided study showed that α-mangostin was the principal constituent. Herein, we reported for the first time the hypouricemic activities and underling mechanism of α-mangostin. The α-mangostin dose- and time-dependently decreased the levels of serum urate in hyperuricemic mice and markedly increased the clearance of urate in hyperuricemic rats, exhibiting a promotion of urate excretion in the kidney. Further evidence showed that α-mangostin significantly decreased the protein levels of GLUT9 in the kidneys. The change in the expression of URAT1 was not observed. Moreover, α-mangostin did not inhibit the activities of xanthine oxidoreductase and uricasein vitroorin vivo. Taken together, these findings suggest that α-mangostin has potential to be developed as a new anti-hyperuricemic agent with promoting uric acid excretion.