Phloroglucinol Derivatives from <i>Dryopteris crassirhizoma</i> as Potent Xanthine Oxidase Inhibitors
<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...
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MDPI AG
2020-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/1/122 |
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| author | Heung Joo Yuk Ji-Yul Kim Yoon-Young Sung Dong-Seon Kim |
| author_facet | Heung Joo Yuk Ji-Yul Kim Yoon-Young Sung Dong-Seon Kim |
| author_sort | Heung Joo Yuk |
| collection | DOAJ |
| description | <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. |
| first_indexed | 2024-03-10T13:41:26Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T13:41:26Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-362c09edae604d428202abc48a114c952023-11-21T02:59:46ZengMDPI AGMolecules1420-30492020-12-0126112210.3390/molecules26010122Phloroglucinol Derivatives from <i>Dryopteris crassirhizoma</i> as Potent Xanthine Oxidase InhibitorsHeung Joo Yuk0Ji-Yul Kim1Yoon-Young Sung2Dong-Seon Kim3Herbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon 34054, KoreaHerbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon 34054, KoreaHerbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon 34054, KoreaHerbal Medicine Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon 34054, Korea<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.https://www.mdpi.com/1420-3049/26/1/122<i>Dryopteris crassirhizoma</i>goutflavaspidic acidphloroglucinolstraditional medicinexanthine oxidase |
| spellingShingle | Heung Joo Yuk Ji-Yul Kim Yoon-Young Sung Dong-Seon Kim Phloroglucinol Derivatives from <i>Dryopteris crassirhizoma</i> as Potent Xanthine Oxidase Inhibitors Molecules <i>Dryopteris crassirhizoma</i> gout flavaspidic acid phloroglucinols traditional medicine xanthine oxidase |
| title | Phloroglucinol Derivatives from <i>Dryopteris crassirhizoma</i> as Potent Xanthine Oxidase Inhibitors |
| title_full | Phloroglucinol Derivatives from <i>Dryopteris crassirhizoma</i> as Potent Xanthine Oxidase Inhibitors |
| title_fullStr | Phloroglucinol Derivatives from <i>Dryopteris crassirhizoma</i> as Potent Xanthine Oxidase Inhibitors |
| title_full_unstemmed | Phloroglucinol Derivatives from <i>Dryopteris crassirhizoma</i> as Potent Xanthine Oxidase Inhibitors |
| title_short | Phloroglucinol Derivatives from <i>Dryopteris crassirhizoma</i> as Potent Xanthine Oxidase Inhibitors |
| title_sort | phloroglucinol derivatives from i dryopteris crassirhizoma i as potent xanthine oxidase inhibitors |
| topic | <i>Dryopteris crassirhizoma</i> gout flavaspidic acid phloroglucinols traditional medicine xanthine oxidase |
| url | https://www.mdpi.com/1420-3049/26/1/122 |
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