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This study aimed to evaluate the phytopharmaceutical compound Moringa isothiocyanate-1 (MIC-1) isolated from hydroalcoholic extract of M. oleifera seeds for the treatment of seizures and anxiety in adult zebrafish. MIC-1 (up to 0.5 mg\/mL) did not show any acute toxic effects over a 96-h period. Moreover, MIC-1 (0.005 and 0.05 mg\/mL) delayed the onset of seizures induced by pentylenetetrazol, indicating anticonvulsant activity. The anticonvulsant effects of MIC-1 (0.05 mg\/mL) were reversed by flumazenil, suggesting a mechanism involving the GABAA receptor. Furthermore, MIC-1 (0.05 mg\/mL) has anxiolytic effects, with involvement of the serotonergic and GABAergic systems. In silico assays confirmed the interaction of MIC-1 with the GABAA, 5-HT1B, 5-HT2A\/C, and 5-HT3A\/B receptors. Additionally, MIC-1 was effective in treating anxiety related to alcohol withdrawal in zebrafish. These findings suggest the pharmacological potential of MIC-1 for the development of new treatments for seizures and anxiety.<\/jats:p>","DOI":"10.3390\/biology15171523","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:10:33Z","timestamp":1788430233000},"page":"1523","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anxiolytic and Anticonvulsant Effects of Moringa Isothiocyanate-1 (MIC-1) in Adult Zebrafish"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5786-899X","authenticated-orcid":false,"given":"Jo\u00e3o Victor Alves","family":"Martins","sequence":"first","affiliation":[{"name":"Postgraduate Program in Nutrition and Health, Health Sciences Center, Laboratory of Endocrine Physiology and Metabolism, State University of Cear\u00e1, Fortaleza 60741-000, Cear\u00e1, 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(2022). An Umbrella Review on the Use of Antipsychotics in Anxiety Disorders: A Registered Report Protocol. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0269772"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Marin, M.C.D., Pedro, M.O.P., Perrotte, G., Martins-da-Silva, A.S., Lassi, D.L.S., Blaas, I.K., Castaldelli, F.I., Brisola Dos Santos, M.B., Kortas, G.T., and Campos, M.W. (2023). Pharmacological Treatment of Alcohol Cravings. Brain Sci., 13.","DOI":"10.3390\/brainsci13081206"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kenda, M., Ko\u010devar Glava\u010d, N., Nagy, M., and Sollner Dolenc, M. (2022). Medicinal Plants Used for Anxiety, Depression, or Stress Treatment: An Update. Molecules, 27.","DOI":"10.3390\/molecules27186021"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1186\/s13287-022-03152-z","article-title":"The Potential of Plant Extracts in Cell Therapy","volume":"13","author":"Li","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jaja-Chimedza, A., Graf, B.L., Simmler, C., Kim, Y., Kuhn, P., Pauli, G.F., and Raskin, I. (2017). Biochemical Characterization and Anti-Inflammatory Properties of an Isothiocyanate-Enriched Moringa (Moringa Oleifera) Seed Extract. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0182658"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e17420","DOI":"10.1016\/j.heliyon.2023.e17420","article-title":"Water Purification Improvement Using Moringa Oleifera Seed Extract Pastes for Coagulation Follow Scoria Filtration","volume":"9","author":"Dandesa","year":"2023","journal-title":"Heliyon"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.phytochem.2014.03.028","article-title":"Stable, Water Extractable Isothiocyanates from Moringa Oleifera Leaves Attenuate Inflammation in Vitro","volume":"103","author":"Waterman","year":"2014","journal-title":"Phytochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sailaja, B.S., Hassan, S., Cohen, E., Tmenova, I., Farias-Pereira, R., Verzi, M.P., and Raskin, I. (2022). Moringa Isothiocyanate-1 Inhibits LPS-Induced Inflammation in Mouse Myoblasts and Skeletal Muscle. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0279370"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100479","DOI":"10.1016\/j.phyplu.2023.100479","article-title":"Isothiocyanate-Rich Moringa Seed Extract Reduces Skin Inflammation in Mouse Ear Edema Model","volume":"3","author":"Wolff","year":"2023","journal-title":"Phytomed. Plus"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Fabisiak, T., and Patel, M. (2022). Crosstalk between Neuroinflammation and Oxidative Stress in Epilepsy. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.976953"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Parsons, A.L.M., Bucknor, E.M.V., Castroflorio, E., Soares, T.R., Oliver, P.L., and Rial, D. (2022). The interconnected mechanisms of oxidative stress and neuroinflammation in epilepsy. Antioxidants, 11.","DOI":"10.3390\/antiox11010157"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111871","DOI":"10.1016\/j.bbr.2019.03.040","article-title":"Anxiolytic-like Effect of Chalcone N-{(4\u2019-[(E)-3-(4-Fluorophenyl)-1-(Phenyl) Prop-2-En-1-One]} Acetamide on Adult Zebrafish (Danio Rerio): Involvement of the GABAergic System","volume":"374","author":"Ferreira","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1021\/jf505014n","article-title":"Direct and Indirect Antioxidant Activity of Polyphenol- and Isothiocyanate-Enriched Fractions from Moringa oleifera","volume":"63","author":"Tumer","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.biopha.2018.08.160","article-title":"Antinociceptive Activity of Ethanolic Extract of Azadirachta Indica A. Juss (Neem, Meliaceae) Fruit through Opioid, Glutamatergic and Acid-Sensitive Ion Pathways in Adult Zebrafish (Danio Rerio)","volume":"108","author":"Batista","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_19","unstructured":"(1992, July 17). OECD Guideline for Testing Acute Toxicity in Fishes, (1992) Test No. Available online: http:\/\/www.oecd.org\/chemicalsafety\/risk-assessment\/1948241.pdf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1089\/zeb.2017.1436","article-title":"Adult Zebrafish (Danio Rerio): An Alternative Behavioral Model of Formalin-Induced Nociception","volume":"14","author":"Santos","year":"2017","journal-title":"Zebrafish"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"105796","DOI":"10.1016\/j.neuint.2024.105796","article-title":"Anticonvulsant and Anxiolytic-like Potential of the Essential Oil from the Ocimum Basilicum Linn Leaves and Its Major Constituent Estragole on Adult Zebrafish (Danio Rerio)","volume":"178","author":"Batista","year":"2024","journal-title":"Neurochem. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.pbb.2011.04.021","article-title":"Effects of Anxiolytics in Zebrafish: Similarities and Differences between Benzodiazepines, Buspirone and Ethanol","volume":"99","author":"Gebauer","year":"2011","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jep.2017.06.012","article-title":"Maerua Angolensis Stem Bark Extract Reverses Anxiety and Related Behaviours in Zebrafish-Involvement of GABAergic and 5-HT Systems","volume":"207","author":"Benneh","year":"2017","journal-title":"J. Ethnopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/nature13293","article-title":"Crystal Structure of a Human GABAA Receptor","volume":"512","author":"Miller","year":"2014","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s10822-007-9133-z","article-title":"Epik: A Software Program for pK(a) Prediction and Protonation State Generation for Drug-like Molecules","volume":"21","author":"Shelley","year":"2007","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"W445","DOI":"10.1093\/nar\/gkq311","article-title":"HexServer: An FFT-Based Protein Docking Server Powered by Graphics Processors","volume":"38","author":"Macindoe","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"106684","DOI":"10.1016\/j.vascn.2020.106684","article-title":"Insights into Toxicology, Safety Pharmacology, and Drug Dependence Testing: The Performance and Predictive Values of Nonclinical Tests","volume":"103","author":"Ciangherotti","year":"2020","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4","DOI":"10.20517\/2572-8180.2017.15","article-title":"Zebrafish as Screening Model for Detecting Toxicity and Drugs Efficacy","volume":"3","author":"Caballero","year":"2018","journal-title":"J. Unexplored Med. Data"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"104921","DOI":"10.1016\/j.yexmp.2024.104921","article-title":"Dexamethasone Attenuates Low-Frequency Brainwave Disturbances Following Acute Seizures Induced by Pentylenetetrazol in Wistar Rats","volume":"139","author":"Ribeiro","year":"2024","journal-title":"Exp. Mol. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1136\/annrheumdis-2019-216114","article-title":"EULAR Recommendations for the Management of Sj\u00f6gren\u2019s Syndrome with Topical and Systemic Therapies","volume":"79","author":"Bombardieri","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.jep.2013.08.006","article-title":"Studies on Neuropharmacological Profile of Ethanol Extract of Moringa Oleifera Leaves in Mice","volume":"149","author":"Bakre","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"114290","DOI":"10.1016\/j.jep.2021.114290","article-title":"Understanding the Effects of Moringa Oleifera in Chronic Unpredictable Stressed Zebrafish Using Metabolomics Analysis","volume":"278","author":"Rosdy","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1080\/13880209.2022.2056207","article-title":"Moringa oleifera seed ethanol extract and its active component kaempferol potentiate pentobarbital-induced sleeping behaviours in mice via a GABAergic mechanism","volume":"60","author":"Liu","year":"2022","journal-title":"Pharm. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1001\/jamapsychiatry.2015.0584","article-title":"Epidemiology of DSM-5 Alcohol Use Disorder: Results From the National Epidemiologic Survey on Alcohol and Related Conditions III","volume":"72","author":"Grant","year":"2015","journal-title":"JAMA Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1111\/acer.14458","article-title":"An Exploratory Factor Analysis of the Stimulant, Sedative, and Affective Responses to Alcohol","volume":"44","author":"Grodin","year":"2020","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105706","DOI":"10.1016\/j.neuint.2024.105706","article-title":"Potential of the Blue Calm\u00ae Food Supplement in the Treatment of Alcohol Withdrawal-Induced Anxiety in Adult Zebrafish (Danio Rerio)","volume":"175","author":"Marques","year":"2024","journal-title":"Neurochem. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9801","DOI":"10.1080\/07391102.2021.1935322","article-title":"Combretum lanceolatum Extract Reverses Anxiety and Seizure Behavior in Adult Zebrafish through GABAergic Neurotransmission: An in Vivo and in Silico Study","volume":"40","author":"Ferreira","year":"2022","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9929805","DOI":"10.1155\/2021\/9929805","article-title":"Involvement of GABAA Receptors in the Anxiolytic-Like Effect of Hydroxycitronellal","volume":"2021","author":"Andrade","year":"2021","journal-title":"Biomed. Res. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"113159","DOI":"10.1016\/j.bbr.2021.113159","article-title":"Role of 5-HT1A and 5-HT2C Receptors of the Dorsal Periaqueductal Gray in the Anxiety- and Panic-Modulating Effects of Antidepressants in Rats","volume":"404","author":"Maraschin","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mitroshina, E.V., Marasanova, E.A., and Vedunova, M.V. (2023). Functional Dimerization of Serotonin Receptors: Role in Health and Depressive Disorders. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216416"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"123830","DOI":"10.1016\/j.jenvman.2024.123830","article-title":"Assessing the Toxicological Impact of PET-MPs Exposure on IVDD: Insights from Network Toxicology and Molecular Docking","volume":"373","author":"Zhang","year":"2025","journal-title":"J. Environ. Manag"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"102396","DOI":"10.1016\/j.sbi.2022.102396","article-title":"Mapping the Binding Sites of Challenging Drug Targets","volume":"75","author":"Wakefield","year":"2022","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Olayanju, J.B., Bozic, D., Naidoo, U., and Sadik, O.A. (2024). A comparative review of key isothiocyanates and their health benefits. Nutrients, 16.","DOI":"10.3390\/nu16060757"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.bbr.2015.12.030","article-title":"Sulforaphane produces antidepressant- and anxiolytic-like effects in adult mice","volume":"301","author":"Wu","year":"2016","journal-title":"Behav. Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1007\/s12035-022-03201-x","article-title":"Protective effect of sulforaphane on oxidative stress and mitochondrial dysfunction associated with status epilepticus in immature rats","volume":"60","year":"2023","journal-title":"Mol. Neurobiol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/17\/1523\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:54:59Z","timestamp":1788584099000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/15\/17\/1523"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":45,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["biology15171523"],"URL":"https:\/\/doi.org\/10.3390\/biology15171523","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}