antidepressant activity of enicostemma littorale blume in shp2 (protein tyrosine phosphatase)‑inhibited animal model of depression

background: the objective of this study is to develop a new animal model based on signaling pathways to understand the pathophysiology, therapy of depression, and to investigate the antidepressant activity of enicostemma littorale which is not yet established. methods: animal models of depression were raised by physical methods and administration of methyl isobutyl ketone (100 mg/kg b.w., i.p.,) and a protein tyrosine phosphatase inhibitor, sodium orthovanadate (30 mg/kg b.w., i.p.,) to young wistar rats. e. littorale aqueous extract (100 mg/kg b.w., oral) was administered. forced swimming test (fst), biochemical, and histopathological parameters were performed with reference to fluoxetine (20 mg/kg b.w., oral) treatment. results: high‑performance thin‑layer chromatography confirmed the presence of swertiamarin, a unique glycoside present in the gentianaceae family. fst indicated high rates of immobility in depressed groups and low rates in plant extract‑administered group with reference to fluoxetine. biochemical assays indicated significantly (p < 0.05) increased levels of total protein, superoxide dismutase, triglycerides, and total serum cholesterol, whereas significant reduction (p < 0.05) of glutathione peroxidase, catalase, and lipid peroxidation in plant extract‑administered groups in comparison to the depressed groups. histopathological analysis indicated disorganized neuronal architecture during depression whereas rejuvenation of neuronal patterns was observed during treatment with plant extract and fluoxetine. conclusions: this study shows that sodium orthovanadate induces depression in animals and also establishes the antidepressant activity of e. littorale.