Electrochemical Analysis and in silico Evaluation of Tamarindus indica Linn Fruit Pulp Extract for Potential Antidepressant Effects

Abstract

Introduction: Depression involves neurotransmitter imbalance, HPA axis dysfunction, neuroinflammation, and impaired neuroplasticity. The limitations of SSRIs and SNRIs have prompted interest in plant-derived alternatives. Tamarindus indica Linn. fruit pulp (TIL-P) contains bioactive compounds with antioxidant, anti-inflammatory, and neuroprotective properties, yet its antidepressant potential is underexplored. Materials and Methods: Water and ethanol extracts were analyzed for phenolic, flavonoid, and tannin content. Electrochemical activity was assessed via Microbial Fuel Cells (MFCs). Network pharmacology identified depression-related targets, and molecular docking evaluated interactions with key proteins, using fluoxetine as a control. Results: Water extract yielded a higher extraction efficiency (28.48%) than ethanol extract (17.34%). Ethanol extract had significantly higher flavonoid content, whereas water extract was richer in condensed tannins. MFC analysis showed the water extract at 2000 ppm had the highest amplification factor (1.51), while ethanol extract activity plateaued beyond 1000 ppm, likely due to organic acid-related bacterial growth inhibition. Network pharmacology identified nine hub genes (GAPDH, EGFR, CTNNB1, IL1B, ALB, SRC, TP53, TNF, AKT1) linked to depressive disorder pathways. Molecular docking revealed that catechin, cyanidin, and Pyran-4-one,2,3-dihydro-3,5-dihydroxy-6-methyl displayed strong binding affinities with ALB and EGFR, in some cases exceeding fluoxetine, indicating potential multi-target antidepressant effects. Discussion: The combined electrochemical, phytochemical, and in silico results suggest that TIL-P contains polyphenolic compounds capable of modulating neuroinflammation, oxidative stress, and neurotransmitter-related signaling mechanistic pathways central to depression pathophysiology. Water extracts appeared more favorable for maximizing electrochemical activity, while ethanol extracts enriched flavonoids with strong docking affinities. These complementary solvent profiles highlight the potential of dual-extraction approaches to harness both tannin- and flavonoid-rich fractions for synergistic antidepressant effects. Conclusion: TIL-P, particularly its water-extracted polyphenolic constituents catechin, cyanidin, and Pyran-4-one,2,3-dihydro-3,5-dihydroxy-6-methyl, shows promise as a natural antidepressant candidate through neuroprotective, antioxidant, and anti-inflammatory mechanisms. These findings support further in vitro and in vivo studies to validate efficacy, safety, and mechanism of action.