Evaluation of Enzyme Inhibition and Kinetic Profiles of Origanum Essential Oils on Metabolic and Central Nervous System Targets

ABSTRACT: Noncommunicable diseases (NCDs) are now the leading cause of death globally, accounting for around 70% of annual mortality, with a particularly severe impact in low-income countries. The genus Origanum L. (Lamiaceae), comprising 43 species distributed worldwide, includes several species traditionally used in ethnomedicine. This study aimed to: (I) identify the chemical composition of essential oils (EOs) from the aerial parts of Origanum vulgare, Origanum majorana, and Origanum heracleoticum by gas chromatography–mass spectrometry (GC–MS); (II) evaluate their antioxidant activity via 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), 2,20-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and FRAP assays; (III) assess their inhibitory effects on enzymes involved in metabolic and central nervous system (CNS) functions; and (IV) determine the inhibition mechanisms of the most active EOs and their main constituents using Michaelis–Menten kinetics. O. vulgare EO, rich in carvacrol and p-cymene, exhibited the highest antioxidant activity and acted as an uncompetitive inhibitor of α-glucosidase. O. majorana EO, dominated by γ-terpinene and terpinen-4-ol, showed the strongest tyrosinase (TYR) inhibition (monophenolase and diphenolase reactions), acting as a mixed-type inhibitor. The EO of O. heracleoticum, characterized by carvacrol, thymol, and γ-terpinene, displayed significant inhibitory activity against acetylcholinesterase (mixed inhibition) and butyrylcholinesterase (competitive inhibition). To date, no studies have reported the effects of O. majorana EO on TYR, α-amylase, or α-glucosidase, nor have comparative studies explored the inhibition of lipase by all three species’ EOs. These findings suggest that Origanum EOs hold promise as multifunctional agents for managing metabolic and CNS disorders, supporting their potential use in pharmaceutical and nutraceutical applications. Highlights: This is the first study to evaluate kinetic inhibition of metabolic and CNS enzymes by Origanum EOs. EOs showed uncompetitive, competitive, and mixed-type inhibition depending on the enzyme.