Target Identification and Mechanistic Analysis of Terpinolene in Atherosclerosis: A Network Pharmacology Approach with Molecular Docking Validation

Abstract The objective of this study is to evaluate the potential targets and mechanisms involved in terpinolene using in-silico/bioinformatics techniques for anti-atherosclerotic effect. Terpinolene was identified through a systematic database search, and oral bioavailability and drug-likeness score were initially assessed. Targets associated with terpinolene, as well as those related to atherosclerosis, were retrieved from online databases. To evaluate the interactions between terpinolene and atherosclerosis, network pharmacology and molecular docking were employed to assess the binding affinity. Based on network pharmacological analysis, a total of 43 overlapping targets between terpinolene and atherosclerosis were identified. Involvement of regulation of lipid localization, regulation of inflammatory function, and lipid metabolism was revealed by functional enrichment analysis. Terpinolene shows strong binding affinity with key target proteins, including RXRα, PPARα, ALOX5, NR1H3, and ESR1, suggesting its potential role in modulating atherosclerotic-related mechanisms. An overview of this study with a pharmacological network analysis approach to evaluate the promising mechanism of terpinolene in the management of atherosclerosis. Evidences from this study suggest that terpinolene has a pivotal effect on atherosclerosis owing to its response on biological targets, including CYP2C19, PLA2G4A, NR1H3, ALOX5, RXRA, and PPARα, which also demonstrates their clinically confirmed approach to atherosclerosis mitigation. Molecular docking analysis indicated that terpinolene could bind effectively with these targets.