{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T21:00:57Z","timestamp":1779310857593,"version":"3.51.4"},"reference-count":59,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Max Zeller Soehne AG, CH-8590 Romanshorn, Switzerland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic stress is a key factor in the development of depression. It leads to hyperactivation of the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis, which in turn increases the formation of glucocorticoids (GCs). Chronically elevated GC levels disrupt neuroplasticity and affect brain lipid metabolism, which may, ultimately, contribute to the development of depression. This study aimed to investigate the effects of the antidepressants St. John\u2019s Wort extract and escitalopram on lipid metabolism in vivo. Therefore, repeated corticosterone injections were used to induce depression-like behavior in rats. Male Sprague\u2013Dawley rats were stressed with corticosterone injections (40 mg\/kg, s.c.) over 22 consecutive days and were concomitantly treated with varying doses of the St. John\u2019s wort extract Ze 117 (30, 90 or 180 mg\/kg, p.o.) or escitalopram (10 mg\/kg, p.o.) and behavioral changes were evaluated using a modified forced swim test. The results indicate that repeated corticosterone injections significantly decreased the latency to first immobility. Furthermore, co-treatment of corticosterone with Ze 117 increased latency to first immobility significantly compared to rats treated with corticosterone alone. To further investigate the biochemical effects of corticosterone-induced stress, as well as the possible counter-regulation by antidepressants, the lipidomes of the plasma and hippocampus samples were analyzed by shotgun mass spectrometry. Corticosterone-induced stress significantly altered key lipid metabolites in the plasma but not in the hippocampal samples. In the hippocampus, however, specific glycerophospholipids such as lysophosphatidylethanolamines (LPEs) increased with escitalopram treatment and with Ze 117, both showing significant correlations with behavioral parameters. In summary, our study shows significant behavioral- and lipidome-altering processes with Ze 117 and escitalopram in rat plasma and hippocampal samples, thereby providing new targets and biomarker ideas for clinical diagnosis and antidepressant intervention.<\/jats:p>","DOI":"10.3390\/ijms252312667","type":"journal-article","created":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T04:02:18Z","timestamp":1732593738000},"page":"12667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["St. John\u2019s Wort Extract Ze 117 and Escitalopram Alter Plasma and Hippocampal Lipidome in a Rat Model of Chronic-Stress-Induced Depression"],"prefix":"10.3390","volume":"25","author":[{"given":"Hendrik","family":"Bussmann","sequence":"first","affiliation":[{"name":"Medical Department, Max Zeller Soehne AG, Seeblickstrasse 4, 8590 Romanshorn, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swen","family":"Bremer","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Nussallee 11, 53115 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Marie","family":"Hernier","sequence":"additional","affiliation":[{"name":"Porsolt SAS, Z.A. de Glatign\u00e9, 53940 Le Genest-Saint-Isle, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5178-7825","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Drewe","sequence":"additional","affiliation":[{"name":"Medical Department, Max Zeller Soehne AG, Seeblickstrasse 4, 8590 Romanshorn, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5595-5144","authenticated-orcid":false,"given":"Hanns","family":"H\u00e4berlein","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Nussallee 11, 53115 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4844-6389","authenticated-orcid":false,"given":"Sebastian","family":"Franken","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, Nussallee 11, 53115 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginie","family":"Freytag","sequence":"additional","affiliation":[{"name":"Division of Molecular Neuroscience, Department of Biomedicine, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland"},{"name":"GeneGuide AG, Birmannsgasse 8, 4055 Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georg","family":"Boonen","sequence":"additional","affiliation":[{"name":"Medical Department, Max Zeller Soehne AG, Seeblickstrasse 4, 8590 Romanshorn, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7516-8789","authenticated-orcid":false,"given":"Veronika","family":"Butterweck","sequence":"additional","affiliation":[{"name":"Medical Department, Max Zeller Soehne AG, Seeblickstrasse 4, 8590 Romanshorn, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1177\/1745691616646305","article-title":"A stage model of stress and disease","volume":"11","author":"Cohen","year":"2016","journal-title":"Perspect. 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