In Silico Molecular Docking and SwissADME Prediction of Cinnamaldehyde Protection Against the PbO Ps ‐Induced Morphological and Histopathological Teratogenicity

BACKGROUND: This study investigated the antiteratogenic effects of cinnamaldehyde against lead oxide nanoparticulate (PbO-Ps)-induced developmental toxicity in chick embryos. METHODS: PbO-Ps were synthesized using a chemical method and characterized by UV-Vis spectroscopy, FTIR, and SEM. Fertilized Gallus gallus domesticus eggs (n = 56) were randomly assigned to four experimental groups: procedural control (sterile normal saline), PbO-Ps (33 μg/egg), PbO-Ps plus low-dose cinnamaldehyde (33 + 33.2 μg/egg), and PbO-Ps plus high-dose cinnamaldehyde (33 + 66.4 μg/egg). Morphological and histopathological outcomes were assessed. ANOVA was performed to compare outcomes among groups. Molecular docking using AutoDock 4.2 evaluated interactions of cinnamaldehyde with apo p110α/p85α, apo p110δ/p85α, and PTEN. Drug-likeness and pharmacokinetic properties were evaluated using SwissADME. RESULTS: ¹, and irregular plate-like particles with apparent sizes of approximately 100-400 nm. On Day 14, PbO-Ps exposure caused growth retardation, limb and craniofacial deformities, and poor feather development. Persistent morphological abnormalities, impaired movement, and poor coordination were observed after Day 21 in the PbO-Ps group compared with controls. Cinnamaldehyde ameliorated these effects, with significantly greater protection observed at the higher dose (p < 0.05). Severe hepatic, neuronal, and cardiac tissue damage was observed following PbO-Ps exposure, whereas cinnamaldehyde reduced histopathological abnormalities in a dose-dependent manner. Molecular docking showed that cinnamaldehyde interacted with all three target proteins, with the strongest binding affinity observed for apo p110α/p85α. CONCLUSIONS: The findings indicate that high-dose cinnamaldehyde significantly mitigated PbO-Ps-induced developmental toxicity and teratogenicity in chick embryos. Further studies, including molecular dynamics simulations and long-term in vivo investigations, are warranted to clarify the underlying protective mechanisms and evaluate post-hatch effects.