BackgroundAcute and chronic stresses affect the salivary glands which are the source of plasma BDNF during stressful conditions. Pumpkin is a medicinal plant with an evident antioxidant, anti-inflammatory and potential antidepressant effects. This work was conducted to assess the impact of chronic unpredictable mild stress (CUMS) on the structure of albino rats’ salivary glands and evaluate the role of pumpkin extract (Pump) in ameliorating this effect. MethodsFour groups (n=10 each) of male albino rats included in this study; the control, CUMS, CUMS+fluoxetine and (CUMS+Pump). Corticosterone, pro-inflammatory cytokines (TNF-α & IL-6) and the oxidant/antioxidant profile were all assessed in the serum. BDNF mRNA level was measured in the salivary glands using qRT-PCR. Histopathological changes of the salivary glands were also assessed. ResultsDepression was confirmed behaviorally and biochemically. Exposure to CUMS significantly (p< 0.001) up-regulated the level of serum corticosterone. CUMS induced degenerative changes in the secretory and ductal system, atrophy of acini and increased apoptosis of the acinar and ductal cells. Both fluoxetine and Pump significantly up-regulated (p<0.001) BDNF expression in the salivary glands and ameliorated the CUMS-induced histopathological alterations in the salivary glands. Pumpkin significantly (p<0.001) increased the serum levels of antioxidant enzymes SOD, GPX and CAT and reduced the serum levels of the pro-inflammatory cytokines TNF-α, IL-6.ConclusionPumpkin ameliorates chronic stress-induced depression in rats by exerting a promising anti-inflammatory, antioxidant and anti-depressant-like effects in rats exposed to CUMS. Pump subsequently improved stress-induced structural changes in the salivary glands that might be due to the glands up-regulation of BDNF expression.Trial registrationNot applicable.