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Traditional antidepressants like duloxetine (Cymbalta\n                    <jats:sup>\u00ae<\/jats:sup>\n                    ) can produce side effects. Natural extracts like\n                    <jats:italic>Coffea canephora<\/jats:italic>\n                    (green coffee) and\n                    <jats:italic>Nigella sativa<\/jats:italic>\n                    (black seeds) have emerged as possible alternative therapies.\u00a0The present study aims to evaluate the antidepressant efficacy of Cymbalta, green coffee, and black seeds in a reserpine-induced rat depression model.\u00a0Thirty adult male albino rats were divided into five groups: (1) Control group, (2) Depression-induced group (reserpine 0.2\u00a0mg\/kg for 14 days, followed by 0.1\u00a0mg\/kg intraperitoneally), (3) Cymbalta-treated group (30\u00a0mg\/kg orally for four weeks), (4) Green coffee-treated group (400\u00a0mg\/kg orally for four weeks), and (5) Black seed-treated group (350\u00a0mg\/kg orally for four weeks). Behavioral tests (FST, Y-maze), neurotransmitter (DA, 5-HT, NE), oxidative stress markers (MDA, NO, GSH), and neuroinflammatory cytokine levels (Iba-1) were analyzed.\u00a0Cymbalta significantly decreased immobility time in FST and Y-maze, restored neurotransmitter balance, reduced oxidative stress, and mitigated neuroinflammation that induced by reserpine. Also, the green coffee and black seeds demonstrated antidepressant effects against the alterations induced by reserpine, the treatment with black seeds exhibiting superior neurochemical and antioxidant benefits compared with green coffee treatment. Cymbalta showed the greatest antidepressant action, but the green coffee and the black seeds presented good neuroprotective and antidepressant activities. These findings suggest that the natural compounds may serve as adjunctive therapies for depression.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s11011-025-01718-3","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T08:55:03Z","timestamp":1763456103000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of the antidepressant potential of Duloxetine, Coffea canephora, and Nigella sativa in a rat depression model"],"prefix":"10.1007","volume":"40","author":[{"given":"Enas S.","family":"Abdel-Baky","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shadia A.","family":"Radwan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faten Mohamed","family":"Abdelhamid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omnia N.","family":"Abdelrhman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"issue":"24","key":"1718_CR1","doi-asserted-by":"publisher","first-page":"6601670","DOI":"10.5897\/AJPP12.897","volume":"7","author":"M Abdel-Rahman","year":"2013","unstructured":"Abdel-Rahman M, Arafa NMS, El-Khadragy MF, Kassab RB (2013) The neuroprotective role of Nigella sativa extract on Ciprofloxacin and Pentylenetetrazole treated rats. 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