Inhibitory Activity of Quercetin 3-<i>O</i>-Arabinofuranoside and 2-Oxopomolic Acid Derived from <i>Malus domestica</i> on Soluble Epoxide Hydrolase
Flavonoids and triterpenoids were revealed to be the potential inhibitors on soluble epoxide hydrolase (sEH). The aim of this study is to reveal sEH inhibitors from Fuji apples. A flavonoid and three triterpenoids derived from the fruit of <i>Malus domestica</i> were identified as querce...
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MDPI AG
2020-09-01
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| author | In Sook Cho Jang Hoon Kim Yunjia Lin Xiang Dong Su Jong Seong Kang Seo Young Yang Young Ho Kim |
| author_facet | In Sook Cho Jang Hoon Kim Yunjia Lin Xiang Dong Su Jong Seong Kang Seo Young Yang Young Ho Kim |
| author_sort | In Sook Cho |
| collection | DOAJ |
| description | Flavonoids and triterpenoids were revealed to be the potential inhibitors on soluble epoxide hydrolase (sEH). The aim of this study is to reveal sEH inhibitors from Fuji apples. A flavonoid and three triterpenoids derived from the fruit of <i>Malus domestica</i> were identified as quercetin-3-<i>O</i>-arabinoside (<b>1</b>), ursolic acid (<b>2</b>), corosolic acid (<b>3</b>), and 2-oxopomolic acid (<b>4</b>). They had half-maximal inhibitory concentration of the inhibitors (IC<sub>50</sub>) values of 39.3 ± 3.4, 84.5 ± 9.5, 51.3 ± 4.9, and 11.4 ± 2.7 μM, respectively, on sEH. The inhibitors bound to allosteric sites of enzymes in mixed (<b>1</b>) and noncompetitive modes (<b>2</b>–<b>4</b>). Molecular simulations were carried out for inhibitors <b>1</b> and <b>4</b> to calculate the binding force of ligands to receptors. The inhibitors bound to the left (<b>1</b>) and right (<b>4</b>) pockets next to the enzyme’s active site. Based on analyses of their molecular docking and dynamics, it was shown that inhibitors <b>1</b> and <b>4</b> can stably bind sEH at 1 bar and 300 K. Finally, inhibitors <b>1</b> and <b>4</b> are promising candidates for further studies using cell-based assays and in vivo cardiovascular tests. |
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| spelling | doaj.art-f2780268b8f14174880d0963f15b89b92023-11-20T14:43:46ZengMDPI AGMolecules1420-30492020-09-012518435210.3390/molecules25184352Inhibitory Activity of Quercetin 3-<i>O</i>-Arabinofuranoside and 2-Oxopomolic Acid Derived from <i>Malus domestica</i> on Soluble Epoxide HydrolaseIn Sook Cho0Jang Hoon Kim1Yunjia Lin2Xiang Dong Su3Jong Seong Kang4Seo Young Yang5Young Ho Kim6Department of Horticultural and Crop Environment, National Institute of Horticultural and Herbal Science, RDA, Wanju 55365, KoreaDepartment of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, KoreaSchool of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Guangzhou 510275, ChinaCollege of Pharmacy, Chungnam National University, Daejeon 34134, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, KoreaFlavonoids and triterpenoids were revealed to be the potential inhibitors on soluble epoxide hydrolase (sEH). The aim of this study is to reveal sEH inhibitors from Fuji apples. A flavonoid and three triterpenoids derived from the fruit of <i>Malus domestica</i> were identified as quercetin-3-<i>O</i>-arabinoside (<b>1</b>), ursolic acid (<b>2</b>), corosolic acid (<b>3</b>), and 2-oxopomolic acid (<b>4</b>). They had half-maximal inhibitory concentration of the inhibitors (IC<sub>50</sub>) values of 39.3 ± 3.4, 84.5 ± 9.5, 51.3 ± 4.9, and 11.4 ± 2.7 μM, respectively, on sEH. The inhibitors bound to allosteric sites of enzymes in mixed (<b>1</b>) and noncompetitive modes (<b>2</b>–<b>4</b>). Molecular simulations were carried out for inhibitors <b>1</b> and <b>4</b> to calculate the binding force of ligands to receptors. The inhibitors bound to the left (<b>1</b>) and right (<b>4</b>) pockets next to the enzyme’s active site. Based on analyses of their molecular docking and dynamics, it was shown that inhibitors <b>1</b> and <b>4</b> can stably bind sEH at 1 bar and 300 K. Finally, inhibitors <b>1</b> and <b>4</b> are promising candidates for further studies using cell-based assays and in vivo cardiovascular tests.https://www.mdpi.com/1420-3049/25/18/4352<i>Malus domestica</i>soluble epoxide hydrolasemixed inhibitornoncompetitive inhibitorbinding pocket |
| spellingShingle | In Sook Cho Jang Hoon Kim Yunjia Lin Xiang Dong Su Jong Seong Kang Seo Young Yang Young Ho Kim Inhibitory Activity of Quercetin 3-<i>O</i>-Arabinofuranoside and 2-Oxopomolic Acid Derived from <i>Malus domestica</i> on Soluble Epoxide Hydrolase Molecules <i>Malus domestica</i> soluble epoxide hydrolase mixed inhibitor noncompetitive inhibitor binding pocket |
| title | Inhibitory Activity of Quercetin 3-<i>O</i>-Arabinofuranoside and 2-Oxopomolic Acid Derived from <i>Malus domestica</i> on Soluble Epoxide Hydrolase |
| title_full | Inhibitory Activity of Quercetin 3-<i>O</i>-Arabinofuranoside and 2-Oxopomolic Acid Derived from <i>Malus domestica</i> on Soluble Epoxide Hydrolase |
| title_fullStr | Inhibitory Activity of Quercetin 3-<i>O</i>-Arabinofuranoside and 2-Oxopomolic Acid Derived from <i>Malus domestica</i> on Soluble Epoxide Hydrolase |
| title_full_unstemmed | Inhibitory Activity of Quercetin 3-<i>O</i>-Arabinofuranoside and 2-Oxopomolic Acid Derived from <i>Malus domestica</i> on Soluble Epoxide Hydrolase |
| title_short | Inhibitory Activity of Quercetin 3-<i>O</i>-Arabinofuranoside and 2-Oxopomolic Acid Derived from <i>Malus domestica</i> on Soluble Epoxide Hydrolase |
| title_sort | inhibitory activity of quercetin 3 i o i arabinofuranoside and 2 oxopomolic acid derived from i malus domestica i on soluble epoxide hydrolase |
| topic | <i>Malus domestica</i> soluble epoxide hydrolase mixed inhibitor noncompetitive inhibitor binding pocket |
| url | https://www.mdpi.com/1420-3049/25/18/4352 |
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