| Summary: | <i>Dryopteris crassirhizoma</i> 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 <i>D. crassirhizoma</i> rhizomes have not been analyzed. Thus, we investigated the major constituents responsible for this effect. Bioassay-guided purification isolated four compounds: flavaspidic acid AP (<b>1</b>), flavaspidic acid AB (<b>2</b>), flavaspidic acid PB (<b>3</b>), and flavaspidic acid BB (<b>4</b>). Among these, <b>1</b> showed the most potent inhibitory activity with a half-maximal inhibitory concentration (IC<sub>50</sub>) value of 6.3 µM, similar to that of allopurinol (IC<sub>50</sub> = 5.7 µM) and better than that of oxypurinol (IC<sub>50</sub> = 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, <b>1</b> showed nearly 4-fold higher efficacy than <b>4</b> (IC<sub>50</sub> = 20.9 µM). Representative inhibitors (<b>1</b>–<b>4</b>) in the rhizomes of <i>D. crassirhizoma</i> 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 <i>D. crassirhizoma</i> could be used to develop nutraceuticals and medicines for the treatment of gout.
|
|---|