Phloroglucinol Derivatives from Dryopteris crassirhizoma as Potent Xanthine Oxidase Inhibitors.
Phloroglucinol Derivatives from Dryopteris crassirhizoma as Potent Xanthine Oxidase Inhibitors.
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DOI：
10.3390/molecules26010122
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发表时间：
2020-12-29
期刊：
影响因子：
--
通讯作者：
Kim DS
中科院分区：
文献类型：
--
作者：
Yuk HJ;Kim JY;Sung YY;Kim DS
鳞毛蕨的根茎在亚洲被用作传统药物。这些根的EtOAc提取物显示出有效的黄嘌呤氧化酶（XO）抑制活性。而D.没有分析过绵马贯众的根茎。因此，我们研究了造成这种效应的主要成分。生物测定引导的纯化分离出四个化合物：黄匹酸AP（1）、黄匹酸AB（2）、黄匹酸PB（3）和黄匹酸BB（4）。其中，1显示出最强的抑制活性，半最大抑制浓度（IC 50）值为6.3 µM，与别嘌呤醇（IC 50 = 5.7 µM）相似，优于XO抑制剂羟嘌呤醇（IC 50 = 43.1 µM）。比较活性筛选表明，C3和C3′上的乙酰基对XO抑制至关重要。例如，1的功效比4高出近4倍（IC 50 = 20.9 µM）。在D.绵马贯众对XO具有可逆的非竞争性抑制作用。此外，通过UPLC-QTOF-MS分析显示，有效的抑制剂在根茎中大量存在。因此，D.可用于开发治疗痛风的保健品和药物。
Dryopteris crassirhizoma rhizomes are used as a traditional medicine in Asia. The EtOAc extract of these roots has shown potent xanthine oxidase (XO) inhibitory activity. However, the main phloroglucinols in D. crassirhizoma rhizomes have not been analyzed. Thus, we investigated the major constituents responsible for this effect. Bioassay-guided purification isolated four compounds: flavaspidic acid AP (1), flavaspidic acid AB (2), flavaspidic acid PB (3), and flavaspidic acid BB (4). Among these, 1 showed the most potent inhibitory activity with a half-maximal inhibitory concentration (IC50) value of 6.3 µM, similar to that of allopurinol (IC50 = 5.7 µM) and better than that of oxypurinol (IC50 = 43.1 µM), which are XO inhibitors. A comparative activity screen indicated that the acetyl group at C3 and C3′ is crucial for XO inhibition. For example, 1 showed nearly 4-fold higher efficacy than 4 (IC50 = 20.9 µM). Representative inhibitors (1–4) in the rhizomes of D. crassirhizoma showed reversible and noncompetitive inhibition toward XO. Furthermore, the potent inhibitors were shown to be present in high quantities in the rhizomes by a UPLC-QTOF-MS analysis. Therefore, the rhizomes of D. crassirhizoma could be used to develop nutraceuticals and medicines for the treatment of gout.
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影响因子：
0.8
作者：
Ren, Qiang;Quan, Xian-gao;Wang, Hui-yun
通讯作者：
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影响因子：
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作者：
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DOI：
10.1124/jpet.104.070433
发表时间：
2004-11-01
影响因子：
3.5
作者：
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通讯作者：
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影响因子：
2.7
作者：
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通讯作者：
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