Mushrooms have a wide existence as food consumption by humans and has been appreciated for their medical attributes in adjuvant therapies. This study strategizes on a comparative mycochemical profiling among elected wild (Daldinia concentrica, Hygrophoropsis aurantiaca) collected from Sirumalai hills and prominent edible mushrooms (Agaricus bisporous, Pleurotus ostreatus). The finest species is scrutinized for extricating its specific compounds by a Gas chromatography–mass spectrometry (GC–MS) analysis. An in silico assay is conducted to evaluate the inhibitory effect of the eluted compounds against depression inducing target and drug efflux proteins [Monoamine oxidase A (MAO-A) and Permeability glycoprotein (P-gp)]. Agaricus bisporous excelled with an elevated mycochemical profile and a compatible antioxidant status. The molecular docking against the target proteins revealed Stigmast-5-EN-3-OL, (MAO-A) and 9-Hexadecenoic acid (P-gp) with minimum binding energy scores of −170.42/−116.6-kcal/mol. This investigation enumerates the therapeutic efficacy of edible mushrooms and establishes its vital nutraceuticals as an antidote against mental ailments.
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