{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:53Z","timestamp":1787029073573,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["2017\/27\/B\/NZ4\/00917"],"award-info":[{"award-number":["2017\/27\/B\/NZ4\/00917"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Imperatorin, a naturally derived furanocoumarin, exerts promising neuropharmacological properties. Therefore, it might be applicable in the treatment of brain diseases such as depression. In the present project, we aimed to investigate the sex-dependent effects of imperatorin (1, 5, and 10 mg\/kg) on behavior and neurochemistry associated with antidepressant effects. The depressive-like behaviors of male and female Swiss mice were investigated in a forced swim test (FST). Subsequently, High-Performance Liquid Chromatography (HPLC) was used to evaluate the level of serotonin, its metabolite, 5-HIAA, and noradrenaline, in mouse brains. The study revealed that only males responded to imperatorin (1 and 5 mg\/kg) treatment and caused an antidepressant effect, such as with respect to depressive-like behaviors, lowering immobility time and increasing immobility latency. The HPLC analysis demonstrated that serotonin levels in the prefrontal cortex of females decreased with the middle dose of imperatorin (5 mg\/kg), while in the male prefrontal cortex, the lower dose (1 mg\/kg) boosted serotonin levels. There were no evident changes observed with respect to noradrenaline and serotonin metabolite levels in the male hippocampus. To conclude, we propose that imperatorin has antidepressant potential, seemingly only in males, influencing brain serotonin level, but the direct mechanism of action requires further investigation.<\/jats:p>","DOI":"10.3390\/molecules27041179","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T04:42:27Z","timestamp":1644468147000},"page":"1179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Imperatorin Influences Depressive-like Behaviors: A Preclinical Study on Behavioral and Neurochemical Sex Differences"],"prefix":"10.3390","volume":"27","author":[{"given":"Joanna","family":"Kowalczyk","sequence":"first","affiliation":[{"name":"Independent Laboratory of Behavioral Studies, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Modestos","family":"Nakos-Bimpos","sequence":"additional","affiliation":[{"name":"Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexia","family":"Polissidis","sequence":"additional","affiliation":[{"name":"Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7528-0487","authenticated-orcid":false,"given":"Christina","family":"Dalla","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Kokras","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"},{"name":"First Department of Psychiatry, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9313-5929","authenticated-orcid":false,"given":"Krystyna","family":"Skalicka-Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Department of Natural Products Chemistry, Medical University of Lublin, 1 Chod\u017aki Street, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Budzy\u0144ska","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Behavioral Studies, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e017173","DOI":"10.1136\/bmjopen-2017-017173","article-title":"Prevalence of depression and depressive symptoms among outpatients: A systematic review and meta-analysis","volume":"7","author":"Wang","year":"2017","journal-title":"BMJ Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s11101-016-9456-2","article-title":"Imperatorin-pharmacological meaning and analytical clues: Profound investigation","volume":"15","year":"2016","journal-title":"Phytochem. 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