Evaluation of Antidepressant Effect of Garcinia indica Fruit Rind Juice inCombination with Gallic Acid: In-silico and In-vivo Studies

Depression is a widespread neuropsychiatric disorder that significantly impairs quality of life and remains a global healthconcern. While conventional antidepressants are effective, their limitations, such as delayed onset and adverse effects,necessitate the exploration of alternative therapies. Garcinia indica (Kokum), traditionally used in Indian medicine,possesses antioxidant and neuroprotective properties, largely attributed to its rich content of polyphenols. The present studyaims to evaluate the antidepressant potential of Garcinia indica fruit rind juice, both alone and in combination with gallicacid, using in-vivo models and molecular docking. The molecular docking (PyRx) study conducted against the MAO-Aenzyme, a bioactive constituent from Garcinia indica, Gartanin, exhibited the highest binding affinity (-8.8 kcal/mol) incomparison with fluoxetine (-7.2 kcal/mol) and gallic acid (-6.3 kcal/mol). In-vivo antidepressant models, Tail SuspensionTest (Group I to V), Forced Swim Test (Groups IA to VA), and biochemical estimation of MAO-A in both in-vivo modelsshowed highly significant reduction (***p < 0.001) in the immobility period and MAO-A levels for the group treated withGallic acid (Group IV and Group IVA, 60mg/kg p.o.) along with Garcinia indica fruit rind juice (5 ml/kg p.o.) and Gallicacid (Group V and Group VA, 60mg/kg p.o.) along with Garcinia indica fruit rind juice (10 ml/kg p.o.). This integratedapproach has validated the synergistic antidepressant potential of Garcinia indica fruit and gallic acid, offering a promising,plant-based adjunct to current antidepressant therapies with reduced side effects.