L. Cucurbita pepo modulates contact dermatitis in depressed rats through downregulation of proinflammatory cytokines and upregulation of antioxidant status

Introduction
To assess the efficacy of pumpkin fruit (Cucurbita pepo L.) extract (PE) in relieving contact dermatitis (CD) in depressed rats compared to a standard treatment of CD and explore the mechanism behind this effect.

Material and methods
Thirty male albino rats were exposed to chronic unpredictable mild stress (CUMS) for 4 weeks for induction of depression, then exposed to 1-fluoro-2,4-dinitrofluorobenzene (DNFB) for 2 weeks for induction of CD. The rats were then divided into 3 groups (n = 10 each); the positive control, Betamethasone-treated, and PE-treated groups. Depression was confirmed by the forced swim test and measuring the serum corticosterone level. Proinflammatory cytokines tumour necrosis factor-a (TNF-a), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were measured in the skin and serum and their mRNA levels were assessed using qRT-PCR. Oxidant/antioxidant profile including levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) was assessed in the skin and serum. Histopathological assessment of skin samples was performed and CD4 and CD68 immunoexpression was assessed.

Results
The used PE included a large amount of oleic acid (about 56%) and a small amount of linoleic acid (about 1%). The topical application of PE significantly attenuated inflammation and oxidative changes attributed to CD associated with chronic stress-induced depression comparable to the standard treatment of CD. PE significantly alleviated signs and histopathological score of CD (p < 0.001) through the significant down-regulation of pro-inflammatory cytokines and the significant up-regulation of antioxidants in the skin. Significant down-regulation (p < 0.001) of TNF-a, IL-6, COX-2 and iNOS gene expression in the PE-treated group confirmed the anti-inflammatory action of PE.

Conclusions
The pumpkin extract, applied topically in CD associated with depression, could be an alternative as well as preventive approach in treating CD. Anti-inflammatory and antioxidants activity of pumpkin is a proposed mechanism behind this effect. Further studies to test this effect on volunteer patients of CD are recommended.