Inhibitory Activity of Natural <i>cis</i>-Khellactone on Soluble Epoxide Hydrolase and Proinflammatory Cytokine Production in Lipopolysaccharides-Stimulated RAW264.7 Cells
The pursuit of anti-inflammatory agents has led to intensive research on the inhibition of soluble epoxide hydrolase (sEH) and cytokine production using medicinal plants. In this study, we evaluated the efficacy of <i>cis</i>-khellactone, a compound isolated for the first time from the r...
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MDPI AG
2023-10-01
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| Series: | Plants |
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| Online Access: | https://www.mdpi.com/2223-7747/12/20/3656 |
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| author | Jang Hoon Kim Ji Hyeon Park Sung Cheol Koo Yun-Chan Huh Mok Hur Woo Tae Park Youn-Ho Moon Tae Il Kim Byoung Ok Cho |
| author_facet | Jang Hoon Kim Ji Hyeon Park Sung Cheol Koo Yun-Chan Huh Mok Hur Woo Tae Park Youn-Ho Moon Tae Il Kim Byoung Ok Cho |
| author_sort | Jang Hoon Kim |
| collection | DOAJ |
| description | The pursuit of anti-inflammatory agents has led to intensive research on the inhibition of soluble epoxide hydrolase (sEH) and cytokine production using medicinal plants. In this study, we evaluated the efficacy of <i>cis</i>-khellactone, a compound isolated for the first time from the roots of <i>Peucedanum japonicum</i>. The compound was found to be a competitive inhibitor of sEH, exhibiting an IC<sub>50</sub> value of 3.1 ± 2.5 µM and <i>k</i><sub>i</sub> value of 3.5 µM. Molecular docking and dynamics simulations illustrated the binding pose of (−)<i>cis</i>-khellactone within the active site of sEH. The results suggest that binding of the inhibitor to the enzyme is largely dependent on the Trp336–Gln384 loop within the active site. Further, <i>cis</i>-khellactone was found to inhibit pro-inflammatory cytokines, including NO, iNOS, IL-1β, and IL-4. These findings affirm that <i>cis</i>-khellactone could serve as a natural therapeutic candidate for the treatment of inflammation. |
| first_indexed | 2024-03-10T20:56:31Z |
| format | Article |
| id | doaj.art-493536581d1441429364479061c6e5da |
| institution | Directory Open Access Journal |
| issn | 2223-7747 |
| language | English |
| last_indexed | 2024-03-10T20:56:31Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-493536581d1441429364479061c6e5da2023-11-19T17:50:06ZengMDPI AGPlants2223-77472023-10-011220365610.3390/plants12203656Inhibitory Activity of Natural <i>cis</i>-Khellactone on Soluble Epoxide Hydrolase and Proinflammatory Cytokine Production in Lipopolysaccharides-Stimulated RAW264.7 CellsJang Hoon Kim0Ji Hyeon Park1Sung Cheol Koo2Yun-Chan Huh3Mok Hur4Woo Tae Park5Youn-Ho Moon6Tae Il Kim7Byoung Ok Cho8Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of KoreaInstitute of Health Science, Jeonju University, 303 Cheonjam-ro, Wansan-gu, Jeonju-si 55069, Jeollabuk-do, Republic of KoreaDepartment of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of KoreaDepartment of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of KoreaDepartment of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of KoreaDepartment of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of KoreaDepartment of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of KoreaDepartment of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Chungcheongbuk-do, Republic of KoreaInstitute of Health Science, Jeonju University, 303 Cheonjam-ro, Wansan-gu, Jeonju-si 55069, Jeollabuk-do, Republic of KoreaThe pursuit of anti-inflammatory agents has led to intensive research on the inhibition of soluble epoxide hydrolase (sEH) and cytokine production using medicinal plants. In this study, we evaluated the efficacy of <i>cis</i>-khellactone, a compound isolated for the first time from the roots of <i>Peucedanum japonicum</i>. The compound was found to be a competitive inhibitor of sEH, exhibiting an IC<sub>50</sub> value of 3.1 ± 2.5 µM and <i>k</i><sub>i</sub> value of 3.5 µM. Molecular docking and dynamics simulations illustrated the binding pose of (−)<i>cis</i>-khellactone within the active site of sEH. The results suggest that binding of the inhibitor to the enzyme is largely dependent on the Trp336–Gln384 loop within the active site. Further, <i>cis</i>-khellactone was found to inhibit pro-inflammatory cytokines, including NO, iNOS, IL-1β, and IL-4. These findings affirm that <i>cis</i>-khellactone could serve as a natural therapeutic candidate for the treatment of inflammation.https://www.mdpi.com/2223-7747/12/20/3656<i>cis</i>-khellactonesoluble epoxide hydrolasecompetitive inhibitormolecular simulationanti-inflammation |
| spellingShingle | Jang Hoon Kim Ji Hyeon Park Sung Cheol Koo Yun-Chan Huh Mok Hur Woo Tae Park Youn-Ho Moon Tae Il Kim Byoung Ok Cho Inhibitory Activity of Natural <i>cis</i>-Khellactone on Soluble Epoxide Hydrolase and Proinflammatory Cytokine Production in Lipopolysaccharides-Stimulated RAW264.7 Cells Plants <i>cis</i>-khellactone soluble epoxide hydrolase competitive inhibitor molecular simulation anti-inflammation |
| title | Inhibitory Activity of Natural <i>cis</i>-Khellactone on Soluble Epoxide Hydrolase and Proinflammatory Cytokine Production in Lipopolysaccharides-Stimulated RAW264.7 Cells |
| title_full | Inhibitory Activity of Natural <i>cis</i>-Khellactone on Soluble Epoxide Hydrolase and Proinflammatory Cytokine Production in Lipopolysaccharides-Stimulated RAW264.7 Cells |
| title_fullStr | Inhibitory Activity of Natural <i>cis</i>-Khellactone on Soluble Epoxide Hydrolase and Proinflammatory Cytokine Production in Lipopolysaccharides-Stimulated RAW264.7 Cells |
| title_full_unstemmed | Inhibitory Activity of Natural <i>cis</i>-Khellactone on Soluble Epoxide Hydrolase and Proinflammatory Cytokine Production in Lipopolysaccharides-Stimulated RAW264.7 Cells |
| title_short | Inhibitory Activity of Natural <i>cis</i>-Khellactone on Soluble Epoxide Hydrolase and Proinflammatory Cytokine Production in Lipopolysaccharides-Stimulated RAW264.7 Cells |
| title_sort | inhibitory activity of natural i cis i khellactone on soluble epoxide hydrolase and proinflammatory cytokine production in lipopolysaccharides stimulated raw264 7 cells |
| topic | <i>cis</i>-khellactone soluble epoxide hydrolase competitive inhibitor molecular simulation anti-inflammation |
| url | https://www.mdpi.com/2223-7747/12/20/3656 |
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