{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:06:50Z","timestamp":1785420410323,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation","doi-asserted-by":"publisher","award":["2022R1A2B5B03001792"],"award-info":[{"award-number":["2022R1A2B5B03001792"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2022R1A2B5B03001792"],"award-info":[{"award-number":["2022R1A2B5B03001792"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Insects"],"abstract":"<jats:p>EpOMEs suppress excessive and unnecessary immune responses at late infection stage in insects. This immune resolvin activity of EpOMEs includes the cell lysis of hemocytes by causing apoptosis. This cytolytic toxicity of EpOMEs suggests a potential insecticidal activity of their stable analogs. In fact, a propoxy derivative of 12,13-EpOME called AS56 mimicked EpOME activity by suppressing immune responses and exhibited insecticidal activity against a lepidopteran insect, Spodoptera exigua. This study evaluated the potency of the EpOME analogs by modifying their functional groups. PD28 is a racemic mixture of propoxy analog at the twelfth carbon. FD25 is a racemic butoxy mixture at the twelfth carbon of AS56. AS61 is saturated at the ninth carbon of AS56. The effects of the EpOME analogs were assessed on two cellular immune responses: hemocyte-spreading and nodule formation. All four analogs inhibited the cellular immune responses; however, AS56 was the most potent in inhibiting the immune responses. FD25 and AS61 were significantly less potent compared to AS56, suggesting crucial roles of the double bond at the ninth carbon and the propoxy chain at the twelfth carbon. The stronger inhibitory activity of AS56 compared to PD28 also suggests the functional role of the stereoisomeric form in physiological functions. The cytotoxicity of AS56 was also the most potent among the analogs, suggesting its insecticidal activity. Subsequent insecticidal bioassays on AS56 toxicity were performed against different insect species. These EpOME analogs were potent against lepidopteran insects (S. exigua and Plutella xylostella) but not against coleopteran (Tenebrio molitor) or thysanopteran (Frankliniella occidentalis) species. Among the EpOME analogs, AS56 was the most toxic against the lepidopteran insects. Spraying AS56 in cabbage fields infested by lepidopteran insects led to acute and high control efficacy against two lepidopteran pests, similar to that of a chemical insecticide, fluxametamide. The AS56-intoxicated larvae exhibited over-excitation in their behavior around 12 h post-treatment. This study indicates that AS56 exhibits an oral toxicity against lepidopteran insects with its cytotoxicity and behavioral over-excitation.<\/jats:p>","DOI":"10.3390\/insects17060588","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T01:23:21Z","timestamp":1780622601000},"page":"588","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chemical Modifications of an Insect Immune Resolvin, EpOME, to a Broad-Spectrum Lepidopteran-Specific Insecticide"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3592-3572","authenticated-orcid":false,"given":"Falguni","family":"Khan","sequence":"first","affiliation":[{"name":"School of Smart-Green, College of Life Sciences & Engineering, Gyeongkuk National University, Andong 36279, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taegeun","family":"Song","sequence":"additional","affiliation":[{"name":"School of Smart-Green, College of Life Sciences & Engineering, Gyeongkuk National University, Andong 36279, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7864-3271","authenticated-orcid":false,"given":"Anders","family":"Vik","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Section for Pharmaceutical Chemistry, University of Oslo, 0371 Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1875-1227","authenticated-orcid":false,"given":"Niayesh","family":"Shahmohammadi","sequence":"additional","affiliation":[{"name":"School of Smart-Green, College of Life Sciences & Engineering, Gyeongkuk National University, Andong 36279, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6840-2167","authenticated-orcid":false,"given":"Yonggyun","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Smart-Green, College of Life Sciences & Engineering, Gyeongkuk National University, Andong 36279, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"591819","DOI":"10.3389\/fendo.2020.591819","article-title":"The biosynthesis of enzymatically oxidized lipids","volume":"11","author":"Hajeyah","year":"2020","journal-title":"Front. Endocrinol."},{"key":"ref_2","first-page":"307","article-title":"Eicosanoids in insects","volume":"Volume 2","author":"Atkinson","year":"2025","journal-title":"Comprehensive Molecular Insect Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101873","DOI":"10.1016\/j.jbc.2022.101873","article-title":"Allosteric regulation by membranes and hydrophobic subsites in phospholipase A2 enzymes determine their substrate specificity","volume":"298","author":"Dennis","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"103743","DOI":"10.1016\/j.dci.2020.103743","article-title":"Deletion mutant of PGE2 receptor using CRISPR-Cas9 exhibits larval immunosuppression and adult infertility in a lepidopteran insect, Spodoptera exigua","volume":"111","author":"Kim","year":"2020","journal-title":"Dev. Comp. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"20183","DOI":"10.1038\/s41598-020-77325-2","article-title":"EpOMEs act as immune suppressors in a lepidopteran insect, Spodoptera exigua","volume":"10","author":"Vatanparast","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105198","DOI":"10.1016\/j.dci.2024.105198","article-title":"Apolipoprotein D3 and LOX product play a role in immune-priming of a lepidopteran insect, Spodoptera exigua","volume":"158","author":"Haraji","year":"2024","journal-title":"Dev. Comp. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"108484","DOI":"10.1016\/j.jnutbio.2020.108484","article-title":"Cytochrome P450-derived linoleic acid metabolites EpOMEs and DiHOMEs: A review of recent studies","volume":"86","author":"Hildreth","year":"2020","journal-title":"J. Nutr. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"106155","DOI":"10.1016\/j.pestbp.2024.106155","article-title":"EpOME mediates the immune resolution and its alkoxide analog enhances the virulence of microbial insecticides against the legume pod borer, Maruca vitrata","volume":"205","author":"Esmaeily","year":"2024","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"104104","DOI":"10.1016\/j.ibmb.2024.104104","article-title":"Insect immune resolution with EpOME\/DiHOME and its dysregulation by their analogs leading to pathogen hypersensitivity","volume":"168","author":"Hrithik","year":"2024","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"002175","DOI":"10.1099\/jgv.0.002175","article-title":"Wild-type and resistance-breaking strains of tomato spotted wilt virus differentially upregulate the immunosuppressive epoxyoctadecamonoenoic acid biosynthesis of its insect vector, Frankliniella occidentalis","volume":"106","author":"Shahmohammadi","year":"2025","journal-title":"J. Gen. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"103290","DOI":"10.1016\/j.ibmb.2019.103290","article-title":"Characterization of the first insect prostaglandin (PGE2) receptor: MansePGE2R is expressed in oenocytoids and lipoteichoic acid (LTA) increases transcript expression","volume":"117","author":"Kwon","year":"2020","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.imlet.2022.05.006","article-title":"Pathogen infection routes and host innate immunity: Lessons from insects","volume":"247","author":"Eleftherianos","year":"2022","journal-title":"Immunol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1146\/annurev.ento.42.1.611","article-title":"Biological mediators of insect immunity","volume":"42","author":"Gillespie","year":"1997","journal-title":"Annu. Rev. Entomol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101434","DOI":"10.1016\/j.cois.2025.101434","article-title":"Recent insights in the development and functions of insect hemocytes","volume":"73","author":"Strand","year":"2026","journal-title":"Curr. Opin. Insect Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e70005","DOI":"10.1002\/arch.70005","article-title":"PGE2 binding affinity of hemocyte membrane preparations of Manduca sexta and identification of the receptor-associated G proteins in two lepidopteran species","volume":"117","author":"Khan","year":"2024","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Khan, F., Jin, G., Esmaeily, M., Haraji, S., Shahmohammadi, N., and Kim, Y. (2025). Functional division of insect blood cells by single-cell RNA-sequencing and cell-type-specific FISH markers. Cells, 14.","DOI":"10.3390\/cells14231842"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Fujinaga, D., Nolan, C., and Yamanaka, N. (2025). Functional characterization of eicosanoid signaling in Drosophila development. PLoS Genet., 21.","DOI":"10.1101\/2025.01.13.632770"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mellentine, S.Q., Brown, H.N., Ramsey, A.S., Li, J., and Tootle, T.L. (2024). Specific prostaglandins are produced in the migratory cells and the surrounding substrate to promote Drosophila border cell migration. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1257751"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1111\/imb.12846","article-title":"Prostaglandin E2 mediates chorion formation of the Asian tiger mosquito, Aedes albopictus, at late oogenesis","volume":"32","author":"Choi","year":"2023a","journal-title":"Insect Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e21949","DOI":"10.1002\/arch.21949","article-title":"PGE2 mediation of egg development in western flower thrips, Frankliniella occidentalis","volume":"112","author":"Choi","year":"2023b","journal-title":"Arch. Insect Biochem. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ibmb.2015.02.004","article-title":"Epoxide hydrolase activities and epoxy fatty acids in the mosquito Culex quinquefasciatus","volume":"59","author":"Xu","year":"2015","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ibmb.2016.06.011","article-title":"Ingestion of the epoxide hydrolase inhibitor AUDA modulates immune responses of the mosquito, Culex quinquefasciatus during blood feeding","volume":"76","author":"Xu","year":"2016","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"108095","DOI":"10.1016\/j.jip.2024.108095","article-title":"Enhanced baculoviral virulence by suppressing the degradation of an insect immune resolvin, epoxyoctadecamonoenoic acid, in three lepidopteran insects","volume":"204","author":"Shahmohammadi","year":"2024","journal-title":"J. Invertebr. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Shahmohammadi, N., Haraji, S., Khan, F., S\u00f8rsk\u00e5r, \u00c5.M., Danielsen, P.E., Vik, A., and Kim, Y. (2025). Antagonistic control of intracellular signals by EpOMEs in hemocytes induced by PGE2 and their chemical modification for a potent insecticide. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0320488"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liu, C., Masri, J., Perez, V., Maya, C., and Zhao, J. (2020). Growth performance and nutrient composition of mealworms (Tenebrio molitor) fed on fresh plant materials-supplemented diets. Foods, 9.","DOI":"10.3390\/foods9020151"},{"key":"ref_26","unstructured":"SAS Institute Inc (1989). SAS\/STAT Users Guide, SAS Institute. [3rd ed.]."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.aspen.2020.03.008","article-title":"Benzylideneacetone and other phenylethylamide bacterial metabolites induce apoptosis to kill insects","volume":"23","author":"Mollah","year":"2020","journal-title":"J. Asia Pac. Entomol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/nm0597-562","article-title":"Bioactivation of leukotoxins to their toxic diols by epoxide hydrolase","volume":"3","author":"Moghaddam","year":"1997","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1165\/ajrcmb.25.4.4104","article-title":"Leukotoxin-diol: A putative toxic mediator involved in acute respiratory distress syndrome","volume":"25","author":"Zheng","year":"2001","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/S0965-1748(97)00046-5","article-title":"Evidence that free fatty acids in trophocytes of Periplaneta americana fat body may be regulated by the activity of phospholipase A2 and cyclooxygenase","volume":"27","author":"Ali","year":"1997","journal-title":"Insect Biochem. Mol. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1006\/gcen.1997.6973","article-title":"Fatty acids stimulate trehalose synthesis in trophocytes of the cockroach (Periplaneta americana) fat body","volume":"108","author":"Ali","year":"1997","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.it.2016.10.001","article-title":"Nociceptor sensory neuron\u2013immune interactions in pain and inflammation","volume":"38","author":"Verri","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Osthues, T., and Sisignano, M. (2019). Oxidized lipids in persistent pain states. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01147"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/nature02196","article-title":"TRP channels as cellular sensors","volume":"426","author":"Clapham","year":"2003","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0092-8674(03)00272-1","article-title":"painless, a Drosophila gene essential for nociception","volume":"113","author":"Tracey","year":"2003","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/ng1513","article-title":"Pyrexia is a new thermal transient receptor potential channel endowing tolerance to high temperatures in Drosophila melanogaster","volume":"37","author":"Lee","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"R123","DOI":"10.1016\/j.cub.2007.12.001","article-title":"TRP channels: It\u2019s not the heat, it\u2019s the humidity","volume":"18","author":"Montell","year":"2008","journal-title":"Curr. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14668","DOI":"10.1073\/pnas.0805041105","article-title":"Distinct TRP channels are required for warm and cool avoidance in Drosophila melanogaster","volume":"105","author":"Rosenzweig","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Insects"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4450\/17\/6\/588\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:00:30Z","timestamp":1780624830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4450\/17\/6\/588"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,4]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["insects17060588"],"URL":"https:\/\/doi.org\/10.3390\/insects17060588","relation":{},"ISSN":["2075-4450"],"issn-type":[{"value":"2075-4450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,4]]}}}