In silico evaluation of Guiera senegalensis phytochemicals as multi-target modulators of anxiety and depression-related proteins

Abstract

Depression and anxiety are prevalent neuropsychiatric disorders with complex etiologies involving multiple neurotransmitter systems. Despite available treatments, limitations such as delayed efficacy, adverse effects, and treatment resistance necessitate the search for safer and more effective alternatives. Guiera senegalensis, a plant widely used in traditional West African medicine, has shown promise for neurological applications, though its bioactive compounds remain underexplored in this context. This study aimed to investigate the antidepressant and anxiolytic potential of phytochemicals from Guiera senegalensis through a comprehensive in silico approach targeting key CNS receptors. Twenty-five bioactive compounds were selected using the IMPPAT and PubChem databases. Target proteins; GABA-A receptor (6HUO), serotonin transporter (5I6X), monoamine oxidase A (2Z5X), and mGluR5 receptor (6FFH), were retrieved from the Protein Data Bank. Molecular docking was conducted using PyRx with AutoDock Vina. SwissADME and ProTox-II were used to evaluate pharmacokinetic properties and predict toxicity endpoints, respectively. Compounds such as Ergostanol (−8.2 kcal/mol), Myricetin (−7.4 kcal/mol), Isorhamnetin (−7.0 kcal/mol), and Quercetin (−7.2 kcal/mol) exhibited strong binding affinities to GABA-A and MAOA, surpassing standard drugs like Zolpidem and Phenelzine. These compounds interacted with key receptor residues essential for neuroactivity. ADME analysis revealed high gastrointestinal absorption and drug-likeness for most candidates, while toxicity predictions indicated favorable safety profiles, with only Myricetin and Quercetin flagged for potential genotoxicity. The findings support the neuropharmacological potential of Guiera senegalensis, identifying several compounds with multi-target affinity, acceptable pharmacokinetics, and low predicted toxicity. These results justify further experimental validation and offer a strong foundation for developing novel phytotherapeutics for anxiety and depression.