Integrating Toxicity Prediction, Protein-Protein Interaction Analysis, and Molecular Docking to Explore the Potential Anti-Atherosclerotic Properties of Crude Palm Oil Minor Constituents

Abstract

Atherosclerosis is a complex cardiovascular disease characterized by lipid accumulation, chronic inflammation, oxidative stress, and endothelial dysfunction. Crude palm oil (CPO) or oil of Elaeis guineensis contains diverse bioactive compounds that may exert protective effects against atherosclerosis. This study aimed to evaluate the anti-atherosclerotic potential of CPO constituents using toxicity prediction, protein-protein interaction (PPI) analysis, and molecular docking. Nineteen compounds identified in CPO were screened for toxicity using ProTox 3.0. Atherosclerosis-related target proteins were identified through literature review and analyzed using the STRING database. Molecular docking was subsequently performed to predict the binding affinity of CPO compounds toward these targets. Toxicity prediction showed that most compounds exhibited low to moderate toxicity, whereas oleic acid was excluded from further analysis due to its predicted high toxicity (LD₅₀ = 48 mg/kg). The PPI network revealed 21 highly interconnected proteins involved in lipid metabolism, inflammation, and vascular homeostasis. Among the evaluated compounds, α-carotene and β-carotene demonstrated the strongest binding affinities toward SCARB1, RSAD2, and CETP. α-Carotene exhibited binding affinities of −16.34, −13.10, and −12.91 kcal/mol, while β-carotene showed affinities of −16.11, −13.14, and −12.42 kcal/mol against SCARB1, RSAD2, and CETP, respectively. Interaction analyses revealed extensive hydrophobic contacts with amino acid residues critical for cholesterol transport, inflammatory signaling, and lipid metabolism. These findings suggest that α-carotene and β-carotene are promising anti-atherosclerotic constituents of CPO and may contribute to cardiovascular protection through modulation of multiple molecular targets involved in atherosclerosis.