Prediction of molecular targets for antidepressant potential of hydroalcoholic extract of Tamarindus indica using network pharmacology approach and evaluating its efficacy in Chronic Unpredictable Mild Stress model in mice

Abstract

The prevalence of psychological disorders has surged since the 1990s, posing a significant global health burden with depressed individuals averaging six lost hours per week and contributing to over 20% of all missed workdays. Current antidepressants, while effective for some, have limited efficacy, dietary restrictions, and adverse effects, including liver damage and hypertension. Natural remedies offer promising therapeutic potential with minimal side effects. Tamarindus indica (TI) is a plant that grows in the shape of a tree. Network pharmacology of TI revealed the key targets MAPK, D1-6, 5HT, DAT, MAO, COMT, PKA, PKC, AKT, and VMAT, which are linked to prominent key pathways such as dopaminergic and serotonergic. The cell viability assays on SH-Sy5y cells indicated a favourable safety profile with an IC50 of 573.99 µg/ml and further, the in vivo efficacy was observed through Chronic Unpredictable Mild Stress (CUMS) model in mice. The hydroalcoholic extract of TI demonstrated antidepressant effects, significantly reducing immobility time in the Tail Suspension Test (TST) and Forced Swim Test (FST). Additionally, locomotor activity, assessed via the Open Field Test (OFT), was significantly increased in the treatment group compared to CUMS mice. Biochemical analyses revealed elevated Brain Derived Neurotropic Factor (BDNF), decreased cortisol levels, and reduced catechol-O-methyltransferase (COMT) concentration in TI-treated (50 mg/kg) groups. These findings underscore the potential of TI as a natural antidepressant, offering a promising avenue for further therapeutic development in depression management. The current study did not evaluate the level of neurotransmitters in the brain, which will be evaluated in future studies.