Headspace Gas Chromatography/Mass Spectrometry Analysis Endorses Melaleuca Species as an Abundant Source of Medicinal Eucalyptol and its Proposed Anti-Obesity Activity

In the present study, the essential oils of Melaleuca bracteata, Melaleuca styphelioides, Melaleuca nesophila, Melaleuca leucadendra, and Melaleuca ericifolia were analyzed via headspace gas chromatography/ mass spectrometry (HS-GC/MS). A consecutive molecular network was constructed via the GNPS (Global Natural Products Social Molecular Networking) for the visual exploration of the volatile constituents among Melaleuca species. The constructed molecular network divulged eucalyptol (1,8 cineole) as the prevailing volatile, especially in M. leucadendra oil. Quantitative estimation of eucalyptol content in the studied species proved M. leucadendra oil as a potential source for its isolation with a content of 6031.8 mu g/g dry weight. In addition, the effect of eucalyptol on the activity of digestive enzymes (alpha-amylase and pancreatic lipase) was assessed. Eucalyptol showed IC50 values of 75.3 +/- 2.1 and 64.6 +/- 1.4 mu g/ml for alpha-amylase and pancreatic lipase inhibition, compared with acarbose and orlistat 34.71 +/- 1.3 and 23.8 +/- 0.82 mu g/ml, respectively with significant difference of p<0.05. Lastly, the molecular docking confirmed the less activity of the eucalyptol towards the tested enzymes revealing the less binding affinity of eucalyptol towards both a-amylase (free binding of energy Delta G = -5.7 Kcal/mol, compared to reference ligand = -8.3 Kcal/mol), and lipase (Delta G = -5.5 Kcal/mol, compared to reference ligand=-6.1Kcal/mol). Further target prediction studies for eucalyptol were applied and proposed the Cytochrome 450 19A1 aromatase enzyme as a possible target of eucalyptol that could be a potential alternative therapy in the management of obesity.