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

Background: 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. Methods: 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. 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 related to fat accumulation was assessed by qRT-PCR. Results: Analyses of the targets revealed that thymol could be potentially involved in the glycolysis/gluconeogenesis and fatty acid degradation pathways. Experiment results in vivo verified that 1 μg/mL and 5 μg/mL thymol treatment significantly reduced lipid deposition in glucose-induced nematodes. The result of qRT-PCR suggested that the decreased level of cpt-1, aco, fabp and tph-1 correlating with β-oxidation in nematodes exposed by 1mM glucose were upregulated after the exposure of thymol. Conclusions: 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, which is potentially used for the treatment of chronic metabolic diseases associated with increased fatty acid deposition.