Anticoagulant activity of Eucalyptus essential oils: An in vitro approach and a bioinformatics-based pharmacokinetic-pharmacodynamic analysis

Coagulation disorders pose significant health risks, requiring effective therapies. Natural products emerge as promising anticoagulant agents, standing out in the search for innovative and safe alternatives, integrating in vitro studies, pharmacological analyses and bioinformatics for therapeutic advances. In this context, a study was conducted on the anticoagulant and toxicological activity of three essential oils of Eucalyptus spp.: Eucalyptus citriodora, Eucalyptus globulus and Eucalyptus staigeriana, commercially acquired. The chemical composition was analyzed by gas chromatography coupled to mass spectrometry. The anticoagulant activity was evaluated by in vitro assays of prothrombin time (PT) and activated partial thromboplastin time (aPTT) at concentrations of 0.19 % to 100 %, performed in triplicate. The mechanism of action was investigated by in silico analysis of activated Factor X, and the toxicological potential was evaluated with bioinformatics tools. The major compound identified was citronellal (57.77 %) in E. citriodora essential oil, eucalyptol (77.03 %) in E. globulus oil, and d-limonene (20.89 %) and geranial (10.54 %) in E. staigeriana oil. E. globulus showed greater anticoagulant efficacy, with prolongation of 256 % in aPTT and 147 % in PT, while the other oils showed prolongation of 117 % in PT. The pharmacokinetic parameters showed similarity with commercial anticoagulants, and the ΔG values in the in-silico model for activated Factor X were comparable to those of warfarin. The results confirm the anticoagulant potential of the three essential oils, especially E. globulus oil, which is more indicated for the prospection of new drugs.