Indirubin-3′-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolase
This study investigated the potential of the indirubin-3′-oxime (I3O) compound to mitigate temperature-induced male infertility in Drosophila melanogaster. Elevated temperatures significantly reduced egg-hatching rates, but I3O supplementation improved these rates, suggesting it can partially restor...
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Taylor & Francis Group
2025-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2024.2447719 |
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| author | Nguyen Viet Phong Hyo-Sung Kim Yan Zhao Eunbyul Yeom Seo Young Yang |
| author_facet | Nguyen Viet Phong Hyo-Sung Kim Yan Zhao Eunbyul Yeom Seo Young Yang |
| author_sort | Nguyen Viet Phong |
| collection | DOAJ |
| description | This study investigated the potential of the indirubin-3′-oxime (I3O) compound to mitigate temperature-induced male infertility in Drosophila melanogaster. Elevated temperatures significantly reduced egg-hatching rates, but I3O supplementation improved these rates, suggesting it can partially restore fertility under heat stress. Additionally, I3O was found to inhibit soluble epoxide hydrolase (sEH), an enzyme involved in the metabolism of epoxyeicosatrienoic acids, which are vital for reproductive health. I3O exhibited sEH inhibitions with an IC50 value of 59.74 ± 0.41 µM. Enzyme kinetics revealed that I3O acts as a non-competitive inhibitor of sEH with a Ki value of 78.88 µM. Molecular docking showed strong interactions between I3O and key residues in the allosteric regions within the sEH enzyme, with a binding affinity of −9.2 kcal/mol. These interactions were supported by 100 ns molecular dynamics simulations, which confirmed the stability of the sEH–I3O complex. |
| format | Article |
| id | doaj-art-bff6d4ec9c474419a3dcf8ac553dc0f6 |
| institution | Kabale University |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-bff6d4ec9c474419a3dcf8ac553dc0f62025-01-22T12:36:54ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742025-12-0140110.1080/14756366.2024.2447719Indirubin-3′-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolaseNguyen Viet Phong0Hyo-Sung Kim1Yan Zhao2Eunbyul Yeom3Seo Young Yang4Department of Biology Education, Teachers College and Institute for Phylogenomics and Evolution, Kyungpook National University, Daegu, Republic of KoreaSchool of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of KoreaSchool of Pharmacy, Yantai University, Yantai, PR ChinaSchool of Life Science and Biotechnology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of KoreaDepartment of Biology Education, Teachers College and Institute for Phylogenomics and Evolution, Kyungpook National University, Daegu, Republic of KoreaThis study investigated the potential of the indirubin-3′-oxime (I3O) compound to mitigate temperature-induced male infertility in Drosophila melanogaster. Elevated temperatures significantly reduced egg-hatching rates, but I3O supplementation improved these rates, suggesting it can partially restore fertility under heat stress. Additionally, I3O was found to inhibit soluble epoxide hydrolase (sEH), an enzyme involved in the metabolism of epoxyeicosatrienoic acids, which are vital for reproductive health. I3O exhibited sEH inhibitions with an IC50 value of 59.74 ± 0.41 µM. Enzyme kinetics revealed that I3O acts as a non-competitive inhibitor of sEH with a Ki value of 78.88 µM. Molecular docking showed strong interactions between I3O and key residues in the allosteric regions within the sEH enzyme, with a binding affinity of −9.2 kcal/mol. These interactions were supported by 100 ns molecular dynamics simulations, which confirmed the stability of the sEH–I3O complex.https://www.tandfonline.com/doi/10.1080/14756366.2024.2447719Indirubin-3′-oximemale infertilityDrosophila melanogastersoluble epoxide hydrolasemolecular dynamics |
| spellingShingle | Nguyen Viet Phong Hyo-Sung Kim Yan Zhao Eunbyul Yeom Seo Young Yang Indirubin-3′-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolase Journal of Enzyme Inhibition and Medicinal Chemistry Indirubin-3′-oxime male infertility Drosophila melanogaster soluble epoxide hydrolase molecular dynamics |
| title | Indirubin-3′-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolase |
| title_full | Indirubin-3′-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolase |
| title_fullStr | Indirubin-3′-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolase |
| title_full_unstemmed | Indirubin-3′-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolase |
| title_short | Indirubin-3′-oxime as a dual-action agent: mitigating heat-induced male infertility in Drosophila melanogaster and inhibiting soluble epoxide hydrolase |
| title_sort | indirubin 3 oxime as a dual action agent mitigating heat induced male infertility in drosophila melanogaster and inhibiting soluble epoxide hydrolase |
| topic | Indirubin-3′-oxime male infertility Drosophila melanogaster soluble epoxide hydrolase molecular dynamics |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2024.2447719 |
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