AUTHOR=Almohaimeed Hailah M. , Hamed Shereen , Seleem Hanan S. , Batawi Ashwaq H. , Mohammedsaleh Zuhair M. , Balgoon Maha Jameal , Ali Soad S. , Al Jaouni Soad , Ayuob Nasra 

TITLE=An Ethanolic Extract of Cucurbita pepo L. Seeds Modifies Neuroendocrine Disruption in Chronic Stressed Rats and Adrenal Expression of Inflammatory Markers and HSP70

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.749766

DOI=10.3389/fphar.2021.749766

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Pumpkins (<italic>Cucurbita pepo</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.</p><p><bold>Objectives:</bold> This study aimed to assess the efficacy of the administration of <italic>Cucurbita pepo</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.</p><p><bold>Materials and Methods:</bold> Forty male albino rats were divided into 4 groups (<italic>n</italic> = 10): control, CUMS, fluoxetine-treated, and CP-treated groups. Behavioral changes, corticosterone level, pro-inflammatory cytokines TNF-α 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.</p><p><bold>Results:</bold> The CP extract significantly reduced the corticosterone level (<italic>p</italic> &lt; 0.001), immobility time (<italic>p</italic> &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 (<italic>p</italic> &lt; 0.001) and significantly upregulated antioxidant levels in the serum.</p><p><bold>Conclusion:</bold><italic>Cucurbita pepo</italic> L. effectively ameliorated the chronic stress-induced behavioral, biochemical, and adrenal structural changes mostly through its antioxidant and anti-inflammatory effects.</p>