Anti-proliferative Activity of Piper trioicum Leaf Essential Oil Based on Phytoconstituent Analysis, Molecular Docking and in silico ADMET Approaches

Background: The essential oils isolated from several medicinal plants have been reported to possess anticancer activities. Both the essential oil and extracts of many Piper species (Piperaceae) possess potential cytotoxic effects against cancer cell lines and are being used in traditional systems of medicine for the treatment of cancer. There is a need to evaluate and validate the anticancer properties of essential oils extracted from other wild species of Piper. Objective: The current research was undertaken to determine the chemical composition and investigate the anti-proliferative activity of wild-growing Piper trioicum leaf essential oil. The selected five major constituents were subjected to molecular docking to identify possible modes of binding against serine/threonine-protein kinase (MST3) protein. Methods: The essential oil of leaf of P. trioicum was extracted by hydrodistillation method, and its chemical composition was evaluated by GC-FID and GC-MS. The anti-proliferative activity of the essential oil was evaluated by the MTT assay against normal (3T3-L1) and various cancer (HCT 116, HT-29, PC-3 and HepG2) cell lines. Molecular docking analysis was performed using the AutoDock 4.2 software. The pharmacokinetic and pharmacodynamic properties of the major constituents were determined using absorption, distribution, metabolization, excretion and toxicity (ADMET) analysis. Results: The GC-MS analysis revealed the identification of 45 constituents with δ-cadinene (19.57 %), germacrene-D (8.54 %), β-caryophyllene (6.84 %), 1-epi-cubenol (4.83 %) and α-pinene (4.52 %) being predominant constituents in the leaf essential oil of P. trioicum. The highest cytotoxicity of essential oil was observed against HT-29 cells (IC50 value of 33.14 μg/ml). 1-epi-cubenol and δ- cadinene exhibited low binding energy values of -6.25 and -5.92 kcal/mol, respectively. For prediction of in silico pharmacokinetic and drug-like properties of the major compounds, the ADMET prediction tool was used, the results of which were observed to be within the ideal range. Conclusion: The present findings demonstrated that P. trioicum essential oil possesses significant anti-proliferative activity and could be effective against cancer treatment.