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尿酸酶、尿酸转运蛋白 1 和有机阴离子转运蛋白 1 介导的 Jacq. ex Wedd. 提取物对高尿酸血症小鼠的降尿酸作用

Hypouricemic Effects of Extracts from Jacq. ex Wedd. in Hyperuricemia Mice through XOD, URAT1, and OAT1.

机构信息

Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

College of Traditional Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao, China.

出版信息

Biomed Res Int. 2020 Jan 29;2020:2968135. doi: 10.1155/2020/2968135. eCollection 2020.

DOI:10.1155/2020/2968135
PMID:32083126
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7011386/
Abstract

L. has been long used for gout in traditional Tibetan medicine and is closely related to the effect of reducing uric acid. This study aimed to investigate the effect of Jacq. ex Wedd. (UW) on lowering uric acid and its mechanism by using HK2 cells and hyperuricemia mouse model. Petroleum ether extract (UWP), ethyl acetate extract (UWE), n-butanol extract (UWB), and alcohol-soluble extract (UWA) from UW were prepared, and HK2 cells were treated with various parts extracts to observe the expression of uric acid transporter at 25, 50, and 100 g/mL for 24 h. Moreover, hyperuricemia mice were administered orally various parts extracts at 0.78 and 2.34 g/kg (crude drug dose converted by extraction rate) to observe the change of hepatic XOD, serum ADA, renal function, and uric acid transporter. experiments showed that UWA can remarkably elevate OAT1 expression and decrease URAT1 expression in HK2 cells. experiments showed that UWP, UWE, UWB, and UWA showed remarkable activity in reducing uric acid, rendering a substantial decline in the SUA level in hyperuricemia mice. Compared with the hyperuricemia and allopurinol groups, UWB and UWA had significant protective effects on renal injury. At the same time, UWA can significantly reduce the activity of XOD and ADA, reduce the expression of URAT1, and increase the expression of OAT1. These results indicated that UWA had an outstanding uric acid lowering effect and did not affect renal function. This may be related to increased uric acid excretion and decreased uric acid production, mediated by renal OAT1, URAT1, liver XOD, and serum ADA. UWA may be a potential drug against hyperuricemia.

摘要

L. 长期以来一直被用于藏医治疗痛风,与降低尿酸的作用密切相关。本研究旨在通过 HK2 细胞和高尿酸血症小鼠模型,探讨 Jacq. ex Wedd.(UW)降低尿酸的作用及其机制。从 UW 中制备石油醚提取物(UWP)、乙酸乙酯提取物(UWE)、正丁醇提取物(UWB)和醇溶性提取物(UWA),用不同部位提取物处理 HK2 细胞,观察 25、50 和 100 μg/mL 条件下 24 h 尿酸转运体的表达。此外,以 0.78 和 2.34 g/kg(按提取物率换算的生药量)给高尿酸血症小鼠口服各部位提取物,观察肝脏 XOD、血清 ADA、肾功能和尿酸转运体的变化。实验表明,UWA 可显著上调 HK2 细胞中 OAT1 的表达,下调 URAT1 的表达。实验表明,UWP、UWE、UWB 和 UWA 均具有显著的降尿酸活性,可显著降低高尿酸血症小鼠的 SUA 水平。与高尿酸血症和别嘌醇组相比,UWB 和 UWA 对肾脏损伤具有显著的保护作用。同时,UWA 可显著降低 XOD 和 ADA 的活性,降低 URAT1 的表达,增加 OAT1 的表达。这些结果表明,UWA 具有显著的降尿酸作用,且不影响肾功能。这可能与肾脏 OAT1、URAT1、肝脏 XOD 和血清 ADA 介导的尿酸排泄增加和尿酸生成减少有关。UWA 可能是一种治疗高尿酸血症的潜在药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/69ca4d93ed4e/BMRI2020-2968135.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/990a369d6c5c/BMRI2020-2968135.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/36ccacba92ad/BMRI2020-2968135.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/701990830db6/BMRI2020-2968135.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/893d8a782caa/BMRI2020-2968135.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/46bfee795d71/BMRI2020-2968135.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/69ca4d93ed4e/BMRI2020-2968135.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/990a369d6c5c/BMRI2020-2968135.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/36ccacba92ad/BMRI2020-2968135.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/701990830db6/BMRI2020-2968135.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/893d8a782caa/BMRI2020-2968135.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/46bfee795d71/BMRI2020-2968135.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9277/7011386/69ca4d93ed4e/BMRI2020-2968135.006.jpg

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