In Silico Evaluation of Nigella sativa Phytocompounds as Potential Modulators of Estrogen Receptor Alpha: A Molecular Docking and ADMET Study

Background: Reproductive dysfunction among women remains a pressing global health issue, often linked to hormonal imbalances involving estrogen receptor alpha (ERα). Nigella sativa has garnered scientific interest due to its diverse phytochemical composition and potential reproductive health benefits. Objective: This study aimed to evaluate selected bioactive compounds from Nigella sativa oil as potential modulators of ERα using advanced computational methods. Methods: A structure-based drug discovery approach was employed. Ten phytocompounds were identified through literature mining and subjected to molecular docking against ERα. Clomiphene citrate, a known selective estrogen receptor modulator (SERM), served as the reference ligand. Binding affinities were analyzed, and pharmacokinetic and toxicity parameters were predicted using ADMET models, including Lipinski's Rule of Five, bioavailability radar, and toxicity risk assessments. Results: Caryophyllene oxide exhibited the strongest binding affinity to ERα (--8.089 kcal/mol), surpassing the reference compound in several pharmacokinetic indices, including oral bioavailability, drug-likeness, and safety profile. While Clomiphene citrate showed superior affinity in isolated docking results, several Nigella sativa compounds demonstrated favorable ADMET characteristics, suggesting enhanced drug development potential. Conclusion: The study underscores the promising pharmacological profile of Nigella sativa phytocompounds, particularly Caryophyllene oxide, as potential ERα modulators. These findings provide a rational basis for further in vitro and in vivo validation, advancing their development as therapeutic candidates for female reproductive disorders.