Exploration of vetiver-derived compounds for addressing remedy against male infertility using in silco approach

BACKGROUND: The rising prevalence of reproductive disorders, including male infertility, necessitates innovative therapeutic strategies. Plant-based extracts, particularly those from Chrysopogon zizanioides (vetiver plant), have emerged as promising candidates. This study employs in silico methodologies to evaluate the therapeutic potential of vetiver-derived compounds against male infertility. This research aims to investigate the pharmacokinetic profiles, bioactivity, toxicity, and molecular interactions of vetiver compounds with proteins implicated in male reproductive health. MATERIALS AND METHODS: The study integrates Absorption, Distribution, Metabolism, and Excretion (ADME) predictions, protein-protein interaction (PPI) analysis, bioactivity and toxicity evaluations, and molecular docking and simulation studies to assess therapeutic viability. ADME tools analyzed the pharmacokinetic profiles of vetiver compounds. Network pharmacology approaches and PPI analysis mapped interactions with target proteins. Bioactivity and toxicity assessments ensured compound safety and efficacy. Molecular docking and simulations examined the binding affinities and dynamic interactions of selected compounds with target proteins. RESULTS: Out of 120 screened compounds, phenolic derivatives were prioritized. Channaine (Ligand-4) exhibited strong therapeutic potential, with 91.2% intestinal absorption, favorable tissue distribution (Vdss: 1.214 log L/kg), and low toxicity (lethal dose 50%: 2.953 mol/kg). Docking revealed strong binding affinities with Nuclear Factor Erythroid 2-Related Factor 2 (NFE2 L2) (-7.4 kcal/mol), Krüppel-like factor (KLF5) (-4.4 kcal/mol), and Nuclear Factor Kappa B Subunit 1 (NFKB 1) (-7.0 kcal/mol). CONCLUSION: Simulations confirmed stable protein-ligand interactions, supporting its therapeutic promise. Vetiver extracts show significant potential for treating male infertility, offering favorable pharmacokinetics, low toxicity, and effective target interactions. These findings warrant further experimental and clinical validation.