<i>In silico</i> anti-inflammatory activity of lavender (<i>Lavandula officinalis</i>) essential oil bioactive compounds: Molecular docking analysis of COX-1 and COX-2, and ADMET prediction

Abstract

<abstract> <p>Advanced investigations are in action worldwide to find medications with improved safety profiles. Natural resources are essential in the creation of innovative treatments and drugs that have fewer side effects. The essential oil (EO) of lavender (<italic>Lavandula officinalis</italic>) is well-known in alternative and complementary therapies for its use as wound-healing and antimicrobial ingredients. However, the exact pharmacological and anti-inflammatory aspects of naturally produced lavender essential oil (LEO) compounds are still unknown. As a consequence, it is essential to explain LEO drug molecular docking experiments with cyclo-oxygenase enzymes (COX-1 and COX-2). An attempt was developed in this study to discover the anti-inflammatory activity of LEO bioactive components. The online DockThor server was used for <italic>in silico</italic> molecule docking simulation. Interaction studies of LEO compound binding poses with COX were performed to get an understanding of the interacting amino acids and their inter-molecular bondings. Based on physicochemical attributes and toxicity, the docked compounds with the greatest binding affinities were also investigated for drug similarity utilizing the admetSAR tool and PASS platforms. Molecular docking studies exploring the bioactive principle targeted action revealed that electrostatic interactions and H-bonds make the main causative factor in inter-molecular connections associated with anti-inflammatory action. Seven top-ranked compounds were selected by virtual screening. Molecular docking revealed that limonene has the highest negative binding affinity (−8.536 kcal/mol) in complex with COX-1, followed by <italic>α</italic>-terpineol (−8.535 kcal/mol) and <italic>p</italic>-cymene (−8.515 kcal/mol), while two approved anti-inflammatory drugs (celecoxib and betamethasone) produced −8.191 and −8.041 kcal/mol respectively. Similarly, these terpenes can be documented as promising drug candidates based on qualifying Lipinski's rule five. The selected terpenes showed excellent drug-like properties and a percentage of human oral absorption. Besides, it was found to be safe for the human body in toxicological risk assessment. This work gives insight into the anti-inflammatory mechanism of action of LEO terpenes. LEO drugs' pharmacokinetic data and molecular docking patterns may open the way for the development of new COX inhibitors with anti-inflammatory capability and improved pharmacokinetic and pharmacodynamic properties.</p> </abstract>