In Silico and In Vivo Studies Reveal the Potential Preventive Impact of Cuminum cyminum and Foeniculum vulgare Essential Oil Nanocapsules Against Depression-like States in Mice Fed a High-Fat Diet and Exposed to Chronic Unpredictable Mild Stress

Hyperlipidemia, oxidative stress, and excessive inflammatory cytokine production are risk factors for depression. The potential preventive effects of essential oils (EOs) such as cumin and fennel EOs on depression may stem from their hypolipidemic, antioxidant, and anti-inflammatory activities. This work aimed to investigate the effects of cumin and fennel EO nanocapsules in a mouse model of depression caused by a high-fat diet (HFD) and chronic mild stress (CMS) using both in silico and in vivo studies. The cumin and fennel EOs were extracted, analyzed by GC-MS, and encapsulated in nano-form using gum Arabic and maltodextrin as wall materials. The freeze-dried nanocapsules were evaluated in HFD/CMS-treated mice. Molecular docking was used to examine the significance of the oils’ compounds in blocking the active sites of hydroxymethylglutaryl-CoA (HMG-CoA) and indoleamine 2,3-dioxygenase (IDO). According to the molecular docking results, the interactions between EO components and HMG-CoA or IDO indicate that these EOs may have hypercholesterolemic and antidepressive effects. Cumin and fennel EO nanocapsules showed hypolipidemic, antioxidant, and anti-inflammatory effects in vivo. This was demonstrated by the down-regulation of oxidants (ROS, MDA, and NO) and inflammatory markers (TLR4, TNF-α, and IL-6) in the brain, changes in lipid profile parameters, and the up-regulation of antioxidant enzymes (SOD, CAT, and GSH). The in silico and in vivo outputs revealed the potential preventive impact of cumin and fennel EO nanocapsules against depression-like states in the mouse model through the prevention of dyslipidemia, neuroxidation, and neuroinflammation. More human studies are needed to fully understand the antidepressive effects of cumin and fennel EO nanocapsules.