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1. Introduction
Stress is an adaptive system that enables human to face and cope with the changing conditions. The intensity and duration of the stressors alter the brain function and structure causing cognitive impairments and depressive episodes (Lee et al., 2021). Previous studies showed an association between cognitive dysfunction and the cortical region (Da Silva et al., 2021).
The brain is susceptible to damage caused by oxidative stress owing to its high oxygen demand and its high content of lipids. Stress elevates oxidative stress and decreases the activity of antioxidant systems in the cortex region (Lowry et al., 2020). Sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) is responsible for the maintenance of Na+ and K+ ions gradients across the cell membrane (Shrivastava et al., 2020). The high amount of reactive oxygen species (ROS) and reactive nitrogen species (RNS), elevated by stress, oxidize the Na+/K+-ATPase α/β subunits causing energy deficit (Liu et al., 2020). The inhibition of the Na+/K+-ATPase activity is associated with neuropsychiatric disorders such as depression (Novaes et al., 2018). Stressors down regulate the anti-inflammatory effect of the parasympathetic nervous system and the hypothalamic–pituitary–gonadal axis causing the fight/flight response. The elevation of pro-inflammatory components is correlated with depression in autoimmune, allergic, cardiovascular and metabolic disorders (Frank et al., 2019). Oxidative stress leads to the induction of the neuroinflammation pathway. Consequently, the etiology of depression involves both the elevation of oxidative stress and pro-inflammatory mediators (Bakunina et al., 2015).
The current antidepressants depend on increasing the monoamine concentration in the synaptic cleft (Erjavec et al., 2021). Unfortunately, nearly 9–33% of patients may develop drug tolerance (Fornaro et al., 2019). This calls the need to targeting new approaches such as inflammatory pathways. Zinc is involved in 70% of the brain protein structure. Therefore, an impairment of zinc homeostasis is associated with depression (Portbury and Adlard, 2017). The severity of depressive symptoms is highly correlated with zinc deficiency (Da Silva et al., 2021). Pumpkin seed oil (PSO) has anti-inflammatory and antioxidant activities due to various bioactive components such as tocopherol, carotenoid, β-sitosterol, flavonoids, unsaturated fatty acids, vitamin E and vitamin C (Kaur et al.,...