Inverse molecular docking reveals a novel function of thymol: inhibition of fat deposition induced by high-dose glucose in Caenorhabditis elegans

As a natural product isolated from thyme oil in thyme, thymol (2-isopropyl-5-methylphenol) harbors antiviral, antioxidant, and other properties, and thus could be potentially used for the treatment of various diseases. However, the function of thymol has not been comprehensively studied. Here, we applied an inverse molecular docking approach to identify unappreciated functions of thymol. Potential targets of thymol in humans were identified by the server of DRAR-CPI, and targets of interest were then assessed by GO and KEGG pathway analysis. Subsequently, homologous proteins of these targets in Caenorhabditis elegans were identified by Blast tool, and their three-dimensional structures were achieved using Swiss-Model workspace. Interaction between thymol and the targeted proteins in worms was verified using AutoDock 4.0. Analyses of the targets revealed that thymol could be potentially involved in the glycolysis/gluconeogenesis and fatty acid degradation pathways. To verify the activity of thymol on lipid deposition in vivo, the C. elegans model was established. The lipid content of nematodes induced by high-dose glucose was determined by Oil Red O and Nile Red staining, and gene expression was assessed by qRT-PCR. The results showed that thymol might lead to the acceleration of β-oxidation by upregulating cpt-1, aco, fabp, and tph-1, causing the descent of lipid content in nematodes. Our findings indicated that thymol could be potentially used for the treatment of chronic metabolic diseases associated with increased fatty acid deposition.