{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:07:32Z","timestamp":1791986852037,"version":"4.4.0"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Russian Scientific Foundation","award":["23-15-20040"],"award-info":[{"award-number":["23-15-20040"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glucocorticoids are metabolized by the CYP3A isoform of cytochrome P450 and by 11-\u03b2-hydroxysteroid dehydrogenase type 1 (11\u03b2-HSD-1). Experimental data suggest that post-traumatic stress disorder (PTSD) is associated with an increase in hepatic 11\u03b2-HSD-1 activity and a concomitant decrease in hepatic CYP3A activity. Trans-resveratrol, a natural polyphenol, has been extensively studied for its antipsychiatric properties. Recently, protective effects of trans-resveratrol were found in relation to PTSD. Treatment of PTSD rats with trans-resveratrol allowed the rats to be divided into two phenotypes. The first phenotype is treatment-sensitive rats (TSR), and the second phenotype is treatment-resistant rats (TRRs). In TSR rats, trans-resveratrol ameliorated anxiety-like behavior and reversed plasma corticosterone concentration abnormalities. In contrast, in TRR rats, trans-resveratrol aggravated anxiety-like behavior and decreased plasma corticosterone concentration. In TSR rats, hepatic 11\u03b2-HSD-1 activity was suppressed, with a concomitant increase in CYP3A activity. In TRR rats, the activities of both enzymes were suppressed. Thus, the resistance of PTSD rats to trans-resveratrol treatment is associated with abnormalities in hepatic metabolism of glucocorticoids. The free energy of binding of resveratrol, cortisol, and corticosterone to the human CYP3A protein was determined using the molecular mechanics Poisson\u2013Boltzmann surface area approach, indicating that resveratrol could affect CYP3A activity.<\/jats:p>","DOI":"10.3390\/ijms24119333","type":"journal-article","created":{"date-parts":[[2023,5,27]],"date-time":"2023-05-27T16:19:37Z","timestamp":1685204377000},"page":"9333","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Resistance to Resveratrol Treatment in Experimental PTSD Is Associated with Abnormalities in Hepatic Metabolism of Glucocorticoids"],"prefix":"10.3390","volume":"24","author":[{"given":"Vadim E.","family":"Tseilikman","sequence":"first","affiliation":[{"name":"Scientific and Educational Center \u2018Biomedical Technologies\u2019, School of Medical Biology, South Ural State University, 454080 Chelyabinsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-9299","authenticated-orcid":false,"given":"Julia O.","family":"Fedotova","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroendocrinology, I.P. Pavlov Institute of Physiology RAS, 6 Emb. Makarova, 199034 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga B.","family":"Tseilikman","sequence":"additional","affiliation":[{"name":"Scientific and Educational Center \u2018Biomedical Technologies\u2019, School of Medical Biology, South Ural State University, 454080 Chelyabinsk, Russia"},{"name":"Faculty of Fundamental Medicine, Chelyabinsk State University, 454001 Chelyabinsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5744-6677","authenticated-orcid":false,"given":"Jurica","family":"Novak","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia"},{"name":"Center for Artificial Intelligence and Cyber Security, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina N.","family":"Karpenko","sequence":"additional","affiliation":[{"name":"Pavlov Department of Physiology, Institute of Experimental Medicine, 197376 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7004-7873","authenticated-orcid":false,"given":"Victoria A.","family":"Maistrenko","sequence":"additional","affiliation":[{"name":"Pavlov Department of Physiology, Institute of Experimental Medicine, 197376 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana S.","family":"Lazuko","sequence":"additional","affiliation":[{"name":"Department of Physiology, Vitebsk State Medical University, Frunze Av. 27, 210023 Vitebsk, Belarus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyudmila E.","family":"Belyeva","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Vitebsk State Medical University, Frunze Av. 27, 210023 Vitebsk, Belarus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustapha","family":"Kamel","sequence":"additional","affiliation":[{"name":"Research, Educational and Innovative Center of Chemical and Pharmaceutical Technologies Chemical Technology Institute, Ural Federal University Named after the First President of Russia B. 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