Essential oil-derived compounds target core fatigue-related genes: A network pharmacology and molecular Docking approach

• Published in: PloS one Vol. 20; no. 5; p. e0314125
• Main Authors: Dakpa, Gyaltsen, Chiang, Yu-Ting, Lin, Li-Yin, Tsao, Nai-Wen, Wang, Chung-Hsuan, Pérez-Sánchez, Horacio, Fernández, Jorge Ricardo Alonso, Wang, Sheng-Yang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.05.2025; Public Library of Science (PLoS)
• Subjects: Acetic acid; Affinity; Analysis; Bcl-2 protein; Binding; Bioactive compounds; Bioavailability; Biocompatibility; Biology and Life Sciences; Bornyl acetate; Cadinol; Cancer therapies; Care and treatment; Chemical properties; Computer and Information Sciences; Drug development; Epidermal growth factor receptors; ErbB Receptors - genetics; ErbB Receptors - metabolism; Essences and essential oils; Essential oils; Fatigue; Genes; Genetic aspects; Health aspects; Herbal medicine; Humans; Hydrogen Bonding; Hydrogen bonds; In vivo methods and tests; Interleukin 6; Interleukin-6 - genetics; Interleukin-6 - metabolism; Ligands; Medicine and Health Sciences; Mitochondrial DNA; Molecular docking; Molecular Docking Simulation; Nervous system; Network Pharmacology; Oils & fats; Oils, Volatile - chemistry; Oils, Volatile - pharmacology; Pharmacology; Physical Sciences; Protein interaction; Protein Interaction Maps - drug effects; Protein-protein interactions; Proteins; Risk factors; Stat3 protein; Therapeutic applications; Toxicity; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0314125

Fatigue is a widespread condition associated with various health issues, yet identifying specific bioactive compounds for its management remains challenging. This study integrates network pharmacology and molecular docking to uncover essential oil-derived compounds with potential antifatigue properties by targeting key genes and molecular pathways. A comprehensive analysis of 872 essential oil compounds was conducted using PubChem, with target prediction via SwissTargetPrediction. The protein-protein interaction (PPI) network and KEGG pathway analysis identified core fatigue-related targets, including ALB, BCL2, EGFR, IL-6, and STAT3, in metabolic dysregulation and inflammatory responses linked to fatigue. Molecular docking exhibits strong binding affinity between key compounds such as Calamenene, T-cadinol, and Bornyl acetate and core targets, suggesting their potential antifatigue effects. However, ADMET analysis confirmed T-cadinol’s drug-likeness, suggesting good bioavailability and minimal toxicity risks. Thus, molecular docking revealed high binding affinity, which was further validated through a 100 ns MD simulation and demonstrated stable interactions with low root mean square deviation (RMSD). Additionally, hydrogen bond analysis confirmed that T-cadinol maintained consistent interactions with key residues such as Thr-790 in EGFR, Arg-222 in ALB, and Arg-104 in IL-6, indicating strong binding stability. While this study provides valuable computational insights, further in vitro and in vivo validation is necessary to confirm these findings and explore potential therapeutic applications.