Phytoconstituents of Exert Benefits for ADHD Conditions by Targeting SLC6A4: Extraction, Spectroscopic Characterization, Phytochemical Screening, , and Computational Perspectives

Attention-deficit/hyperactivity disorder (ADHD) is a persistent neurodevelopmental disorder. Despite pharmacological interventions, there is a need for effective lead molecules and therapeutic targets. Recently, (HE) has been traditionally reported to treat various diseases. Herein, we aimed to explore the noncytotoxic properties, phytochemical composition, and spectroscopic characterization of HE aqueous extract. Additionally, we used computational workflows to identify key therapeutic targets for ADHD and assess HE extract phytoconstituents for potential targeting. Initially, the HE aqueous extract was obtained using Soxhlet extraction, and its cytotoxicity was assessed on SH-SY5Y cells using MTT assays. FTIR spectroscopy characterized the extract's functional groups, while biochemical methods and GC-MS identified its phytochemical constituents. A protein-protein interaction network identified ADHD targets, and molecular docking, dynamics, and QM/MM calculations were used to find potential drug candidates from the HE extract. As a result, the HE extract exhibited no cytotoxicity in SH-SY5Y cells across concentrations (0.625 to 10 μg/mL) after 24 h. FTIR spectroscopic analysis detected 13 different functional groups that hold diverse biological importance. Qualitative phytochemical screening revealed the presence of carbohydrates, flavonoids, anthocyanins, tannins, alkaloids, saponins, steroids, and phenolic compounds. GC-MS profiling identified 17 diverse metabolites. Simultaneously, ADHD-related genes and known therapeutic protein targets were integrated into a network, identifying SLC6A4 as a hub target. Molecular docking of HE extract compounds showed myo-inositol's high binding efficiency (-6.53 kcal/mol). Dynamic simulations demonstrated stable interactions, and QM/MM analysis confirmed myo-inositol's ability to transfer electrons, reinforcing its interaction potential. Overall, the HE aqueous extract shows a potent nontoxic profile and contains phytoconstituents like myo-inositol, offering promising therapeutic potential by targeting SLC6A4 for ADHD.