Peer Review Report For: Unveiling the Fertility Potential of Brassica oleracea: In Silico and In vivo Insights into Protein Kinase B (PKB/AKT1) and Epidermal Growth Factor Receptor (EGFR) Inhibition [version 1; peer review: 1 approved with reservations]
Résumé fourni par la source
Background Infertility is a global health issue, with male factor infertility contributing to nearly 50% of cases. Dysregulation of Protein Kinase B (PKB/AKT1) and Epidermal Growth Factor Receptor (EGFR) signaling impairs spermatogenesis. Bioactive compounds offer promising alternatives for targeting these pathways. Brassica oleracea var. viridis (collard greens) contains phytochemicals with antioxidant and anti-inflammatory properties, suggesting potential reproductive benefits. Objective This study evaluates bioactive compounds from B. oleracea var. viridis as AKT1 and EGFR inhibitors through molecular docking and in vivo validation in a cimetidine (Cemet ®)-induced reproductive toxicity model. Methods Bioactive compounds were identified via Gas Chromatography-Mass Spectrometry and analyzed for physicochemical, pharmacokinetic, and pharmacodynamic properties. Molecular docking assessed binding affinity to AKT1 and EGFR, followed by in vivo validation in cimetidine-exposed Wistar rats. Effects of ethanol extracts and solvent fractions on sperm motility, viability, morphology, count, and agglutination were examined. Results Gamma-sitosterol showed the strongest binding affinity to AKT1 (-8.0 kcal/mol) and EGFR (-6.5 kcal/mol), comparable to co-crystallized ligands. Computational analysis indicated high Gastro-intestinal absorption and low toxicity for most compounds. In vivo, B. oleracea extracts significantly improved sperm motility, viability, and count, mitigating cimetidine-induced toxicity. Ethanol Leaf Extract of Brassica Oleracea (ELEBO), AFBO (Aqueous fractions of brassica Oleracea) and BFBO (n- Butanol fractions of brassica Oleracea) fractions had the most pronounced protective effects, reducing sperm abnormalities and agglutination. Conclusion B. oleracea var. viridis bioactive compounds show spermatoprotective effects, likely via AKT1 and EGFR inhibition. These findings support further research into B. oleracea derivatives for male reproductive health applications.