Multi‐Target Mechanisms of Moroccan Aphrodisiac Plants: An Integrative Computational and Phytochemical Investigation

Abstract

ABSTRACT This integrative study investigates predicted multi‐target mechanisms of Moroccan medicinal plants traditionally used as aphrodisiacs by combining ethnopharmacology, phytochemistry, molecular docking, ADMET filtering, molecular dynamics (MD), and MM/GBSA analyses. A rigorous review identified 33 pharmacologically validated species (20 families) and curated 94 phytochemicals selected according to reported abundance, recurrence in phytochemical studies, and relevance to documented sexual‐health bioactivities. Docking against PDE5, androgen receptor (AR), estrogen receptor‐alpha (ERα), and aromatase highlighted top‐scoring representatives: lutein (PDE5, −10.6 kcal/mol), baicalein (AR, −9.5 kcal/mol), liquiritigenin (ERα, −9.2 kcal/mol), and procyanidins/diosgenin (aromatase, −9.7 kcal/mol). The best‐ranked ligand for each protein was examined to describe interaction fingerprints involving hydrogen‐bond anchoring, hydrophobic packing, and π‐mediated stabilization. Because docking scores alone are insufficient to infer biological activity, the two endocrine hits with favorable docking and acceptable developability profiles, liquiritigenin‐ERα and baicalein‐AR, were further evaluated by 200 ns MD simulations and MM/GBSA calculations using 100 snapshots from the equilibrated 175–200 ns window. These analyses supported time‐dependent complex stability and favorable predicted binding free energies. SwissADME and ADMET‐AI profiling indicated that many candidates occupy a drug‐like physicochemical range, but also flagged important solubility and formulation constraints for highly lipophilic or highly polar chemotypes. Overall, the results provide computational hypotheses for prioritizing Moroccan aphrodisiac phytochemicals; experimental validation through enzyme inhibition assays, receptor/cell‐based studies, and pharmacokinetic/safety testing is required before pharmacological or clinical conclusions can be drawn.