{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:45:34Z","timestamp":1791272734779,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2023R110"],"award-info":[{"award-number":["PNURSP2023R110"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>The first-generation antihistamine chlorpheniramine (CPA) is believed to have both anxiolytic and antidepressant properties. The current study sought to assess the mechanisms behind the antidepressant and anxiolytic effects of CPA therapy concerning oxidative stress, inflammation, and nuclear factor p45 for erythroid 2-Brain-derived neurotrophic factor (Nrf2-BDNF) signaling pathway in forced swimming-induced depressive-like behavior and anxiety. Eighteen male Wistar rats (180\u2013200 gm) rats were separated into three groups (n = 6): a stressed group (acute stress) that underwent the forced swimming test (FST) and a stressed group that received pretreatment with CPA (10 mg\/kg body weight) for 3 weeks (CPA + acute stress). Animals were subsequently put through the following behavioral tests after undergoing a forced swim test (FST) for 5 min: an immobility test, open field test, and elevated plus maze test. Serum cortisol levels were measured when the rats were euthanized at the end of the experiments. Brain neurotransmitters (cortisol, serotonin, and noradrenaline), oxidative stress (SOD and MDA), inflammatory (IL-6 and IL-1) biomarkers, and the Nrf2-BDNF signaling pathway in the hippocampus and cerebral cortex tissues was determined. CPA prevented stress-induced increases in cortisol levels (p &lt; 0.0001), decreased brain neurotransmitters, and increased oxidative stress and inflammation. CPA also upregulated the Nrf2-BDNF signaling pathway. Thus, CPA mitigates depressive-like behavior and anxiety by inhibiting oxidative stress and inflammation and upregulating the Nrf2-BDNF signaling pathway in the brain tissues.<\/jats:p>","DOI":"10.3390\/cimb45080407","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T09:28:34Z","timestamp":1691141314000},"page":"6449-6465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Forced Swimming-Induced Depressive-like Behavior and Anxiety Are Reduced by Chlorpheniramine via Suppression of Oxidative and Inflammatory Mediators and Activating the Nrf2-BDNF Signaling Pathway"],"prefix":"10.3390","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9149-7726","authenticated-orcid":false,"given":"Hasan S.","family":"Alamri","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, King Khalid University, P.O. Box 641, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana","family":"Mufti","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8840-8791","authenticated-orcid":false,"given":"Deema Kamal","family":"Sabir","sequence":"additional","affiliation":[{"name":"Department of Medical-Surgical Nursing, College of Nursing, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulwahab A.","family":"Abuderman","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, P.O. Box 11942, Al-Kharj 16278, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7646-0909","authenticated-orcid":false,"given":"Amal F.","family":"Dawood","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box. 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4250-0818","authenticated-orcid":false,"given":"Asmaa M.","family":"ShamsEldeen","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo 11566, Egypt"},{"name":"Department of Physiology, Faculty of Medicine, October 6 University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0990-8093","authenticated-orcid":false,"given":"Mohamed A.","family":"Haidara","sequence":"additional","affiliation":[{"name":"Department of Physiology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esma R.","family":"Isenovic","sequence":"additional","affiliation":[{"name":"Department of Radiobiology and Molecular Genetics, \u201cVIN\u010cA\u201d Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0806-4442","authenticated-orcid":false,"given":"Mahmoud H.","family":"El-Bidawy","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Medicine, Prince Sattam Bin Abdulaziz University, P.O. Box 11942, Al-Kharj 16278, Saudi Arabia"},{"name":"Department of Physiology, Kasr Al-Aini Faculty of Medicine, Cairo University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1007\/s12094-019-02123-w","article-title":"Coping strategies and depressive symptoms in cancer patients","volume":"22","author":"Ghanem","year":"2020","journal-title":"Clin. Transl. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.physbeh.2015.04.019","article-title":"Behavioral consequences of predator stress in the rat elevated T-maze","volume":"146","author":"Bulos","year":"2015","journal-title":"Physiol. 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