In silico analysis of Ziziphus mauritiana Lam. bioactive compounds targeting GABA receptor and ADMET profiles for potential postpartum depression treatment

Context: Postpartum depression (PPD) affects 10–20% of women and has been associated with disruptions in neurotransmitter systems, neuroinflammation, and oxidative stress. Ziziphus mauritiana contains several bioactive compounds, including quercetin, which have demonstrated neuroprotective potential. Aims: To to predict the binding interactions of Z. mauritiana bioactive compounds with the GABA receptor, analyze their ADMET properties to evaluate their pharmacokinetic and toxicity profiles, and explore their therapeutic potential for PPD through in silico-based drug discovery methodologies. Methods: Molecular docking simulations were performed to assess the interaction of quercetin and other Z. mauritiana compounds with key PPD-related targets, including the GABA_A receptor, BDNF, IL-6, and TNF-α. Fluoxetine and diazepam were used as reference drugs. Docking reliability was validated using RMSD analysis. ADMET profiling was conducted to evaluate drug-likeness, pharmacokinetics, and safety based on Lipinski’s Rule of Five. Results: Quercetin exhibited strong binding affinity to the GABA_A receptor (-7.0 kcal/mol), comparable to diazepam (-7.2 kcal/mol), and showed interactions with other neuroinflammatory markers. ADMET predictions supported its potential for good oral bioavailability and a favorable safety profile. Conclusions: The findings suggest that Z. mauritiana bioactive compounds, particularly quercetin, hold promise as natural therapeutic agents for PPD via multi-target mechanisms. Their ability to modulate neurotransmission and inflammation supports further in vivo and clinical research to validate efficacy and safety in postpartum depression treatment.