Anti-depressant like effects of Aethoscytus foveolus oil by improving stress-mediated alterations of monoamine oxidase, oxidative stress, and neuroinflammation in-vivo

Abstract

Background: Depression is a neuropsychological disorder with a complex pathophysiology and its pharmacotherapy is compromised with adverse side effects. Addressing the need for effective treatment for depression, the current study aims to characterize the antidepressant activity of oil extract derived from Aethoscytus foveolus, bugs that are widely available in India, in a mice model of stress-induced depression. Approach and Results: Chemical moieties characterized by GC-MS of A. foveolus oil extract have shown good affinity for monoamine oxidase A (MAO-A) in-silico. In-vitro MAO-inhibitory assay using mouse brain homogenates also showed similar results at IC50 1.363 nM (R2=0.981, SD±0.05, n=3) of it. These results encouraged us to investigate the antidepressant potential of this oil extract in vivo. Stress-exposed mice (Swiss Albino, either sex, 25-30 gm) were administered 5 and 10 mg/kg doses of oil extract and classified as separate groups (N=6 per group). Behavioral tests like the forced-swim test, tail-suspension test, and open-field test demonstrated significant attenuation of stress-induced depressive-like behaviors in mice by both doses (p<0.0001 with positive control group i.e., stress group), while biochemical tests on mice brain tissues showed amelioration of stress-induced hyperactivation of MAO (p<0.0001) and oxidative stress (by increasing Superoxide dismutase and catalase, while reducing lipid peroxidase and nitric oxide) (p<0.0001). The altered mRNA expression of proinflammatory cytokines (NF-𝜅B, IL-6, IL-12, and TNF-α) (p<0.015) was also improved by this oil extract. In addition, histopathology of hippocampus tissues of mice supports that this oil recovers stress-mediated structural changes of the brain. Conclusion: Our findings suggest that oil derived from A. foveolus could be beneficial in the alleviation of stress-mediated depressive-like behaviors of mice, and in our knowledge, this is the first report identifying anti-neurodegenerative potential of A. foveolus.