Inhibition of 3,5,2′,4′-Tetrahydroxychalcone on Production of Uric Acid in Hypoxanthine-Induced Hyperuricemic Mice
Inhibition of 3,5,2′,4′-Tetrahydroxychalcone on Production of Uric Acid in Hypoxanthine-Induced Hyperuricemic Mice
复制标题
3,5,2',4'-四羟基查尔酮对次黄嘌呤诱导的高尿酸血症小鼠尿酸产生的抑制作用
DOI：
10.1248/bpb.b17-00655
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发表时间：
2018-01-01
影响因子：
2
通讯作者：
Li, Ling
中科院分区：
文献类型：
--
作者：
Niu, Yanfen;Zhou, Yuanfang;Li, Ling
3,5,2',4'-四羟基查耳酮降低尿酸水平的机制尚不清楚。在此，我们研究了3,5,2',4'-四羟基查耳酮对低黄嘌呤诱导的高尿酸血症小鼠尿酸盐水平、黄嘌呤氧化酶/黄嘌呤脱氢酶（XOD/XDH）活性的影响，以及3,5,2',4'-四羟基查耳酮对磷酸核糖焦磷酸合成酶（PRPS）、磷酸核糖基mRNA表达水平和含量的影响。焦磷酸酰胺转移酶（PRPPAT）和次黄嘌呤鸟嘌呤磷酸核糖转移酶（HGPRT）。我们的结果表明，3,5,2',4'-四羟基查尔酮（1.0、2.0 和 4.0 mg/kg）以剂量和时间依赖性方式降低高尿酸血症小鼠血清中的尿酸水平。 3,5,2',4'-四羟基查尔酮也显着抑制血清和肝脏中XOD/XDH的活性；此外，3,5,2',4'-四羟基查尔酮降低了脑中HGPRT mRNA的表达以及肝脏中PRPS和PRPPAT的含量。这些发现表明，3,5,2',4'-四羟基查耳酮通过影响嘌呤核苷酸代谢中的关键酶 XOD/XDH、PRPS、PRPPAT 和 HGPRT 来抑制尿酸产生。
The mechanism of 3,5,2',4'-tetrahydroxychalcone on lowing urate level is still unknown. Here we investigated the effects of 3,5,2',4'-tetrahydroxychalcone on urate levels, xanthine oxidase/xanthine dehydrogenase (XOD/XDH) activities in hypoxanthine-induced hyperuricemic mice, as well as the effects of 3,5,2',4'-tetrahydroxychalcone on the mRNA expression levels and content of phosphoribosyl pyrophosphate synthetase (PRPS), phosphoribosyl pyrophosphate amidotransferase (PRPPAT) and hypoxanthine-guanine phosphoribosyl transferase (HGPRT). Our results demonstrated that 3,5,2',4'-tetrahydroxychalcone (1.0, 2.0, and 4.0 mg/kg) reduced the uric acid levels in serum of the hyperuricemic mice in dose-and time-dependent manners. The activities of XOD/XDH in serum and liver were also significantly inhibited by 3,5,2',4'-tetrahydroxychalcone; In addition, 3,5,2',4'-tetrahydroxychalcone decreased the mRNA expression of HGPRT in brain and content of PRPS and PRPPAT in liver. These findings demonstrated that 3,5,2',4'-tetrahydroxychalcone suppresses uric acid production by affecting the critical enzymes, XOD/XDH, PRPS, PRPPAT and HGPRT in purine nucleotide metabolism.