{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:40:45Z","timestamp":1780404045539,"version":"3.54.1"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"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","id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Pumpkins (<jats:italic>Cucurbita pepo<\/jats:italic> L.) were described to have antioxidant, anti-inflammatory, anti-fatigue, and antidepressant-like effect. The adrenal gland is an important stress-responsive organ that maintains homeostasis during stress.<\/jats:p><jats:p><jats:bold>Objectives:<\/jats:bold> This study aimed to assess the efficacy of the administration of <jats:italic>Cucurbita pepo<\/jats:italic> L. (CP) extract in relieving behavioral, biochemical, and structural changes in the adrenal gland induced by exposure to chronic unpredictable mild stress (CUMS) and to explore the mechanism behind this impact.<\/jats:p><jats:p><jats:bold>Materials and Methods:<\/jats:bold> Forty male albino rats were divided into 4 groups (<jats:italic>n<\/jats:italic> = 10): control, CUMS, fluoxetine-treated, and CP-treated groups. Behavioral changes, corticosterone level, pro-inflammatory cytokines TNF-\u03b1 and IL-6, and oxidant\/antioxidant profile were assessed in the serum at the end of the experiment. Adrenal glands were processed for histopathological and immunohistochemical assessment. Gene expression of caspase-3 and Ki67 and heat shock protein 70 (HSP70) were assessed in adrenal glands using RT-PCR.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> The CP extract significantly reduced the corticosterone level (<jats:italic>p<\/jats:italic> &amp;lt; 0.001), immobility time (<jats:italic>p<\/jats:italic> &amp;lt; 0.001), and inflammatory and oxidative changes associated with CUMS-induced depression compared to the untreated group. The CP extract alleviated CUMS-induced adrenal histopathological changes and significantly reduced apoptosis (<jats:italic>p<\/jats:italic> &amp;lt; 0.001) and significantly upregulated antioxidant levels in the serum.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold><jats:italic>Cucurbita pepo<\/jats:italic> L. effectively ameliorated the chronic stress-induced behavioral, biochemical, and adrenal structural changes mostly through its antioxidant and anti-inflammatory effects.<\/jats:p>","DOI":"10.3389\/fphar.2021.749766","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T10:50:13Z","timestamp":1636541413000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["An Ethanolic Extract of Cucurbita pepo L. Seeds Modifies Neuroendocrine Disruption in Chronic Stressed Rats and Adrenal Expression of Inflammatory Markers and HSP70"],"prefix":"10.3389","volume":"12","author":[{"given":"Hailah M.","family":"Almohaimeed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shereen","family":"Hamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan S.","family":"Seleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashwaq H.","family":"Batawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhair M.","family":"Mohammedsaleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha Jameal","family":"Balgoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soad S.","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soad","family":"Al Jaouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasra","family":"Ayuob","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"14","DOI":"10.4236\/ijamsc.2016.41002","article-title":"Application of GC\/EIMS in Combination with Semi-empirical Calculations for Identification and Investigation of Some Volatile Components in Basil Essential Oil","volume":"4","author":"Abd-El-Kareem","year":"2016","journal-title":"Ijamsc"},{"key":"B2","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1080\/10520295.2017.1323276","article-title":"The Antidepressant-like Effect of Ocimum Basilicum in an Animal Model of Depression","volume":"92","author":"Ali","year":"2017","journal-title":"Biotech. 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