Linking Chemical Profile to Enzyme Inhibition: A Comprehensive Bio-Guided Study of Lippia origanoides Kunth Essential...

Lippia origanoides Kunth (Verbenaceae family), popularly known in northern Brazil as "Salva-de-Marajó", is a native plant widely used in traditional medicine and cooking. While previous studies have addressed its antimicrobial and insecticidal properties, its ability to inhibit disease-related enzymes has received limited attention. This study investigated the essential oil (EO) of L. origanoides as a source of enzyme inhibitors relevant to Alzheimer's disease, metabolic disorders and skin pigmentation disorders. The EO showed strong inhibitory activity against acetylcholinesterase (IC₅₀: 22.9 μg/mL) and α-glucosidase (IC₅₀: 14.6 μg/mL), indicating potential for managing neurodegenerative conditions and diabetes, respectively. Moderate inhibition was observed for lipase, butyrylcholinesterase and tyrosinase. Although carvacrol, the major EO constituent, contributed significantly to these effects, it did not fully explain the observed bioactivity. Bio-guided fractionation revealed that oxygenated compounds were mainly responsible for inhibiting cholinesterases and lipase, whereas α-glucosidase inhibition was associated with hydrocarbon compounds. Both fractions contributed to tyrosinase inhibition, reinforcing the EO's relevance for treating hyperpigmentation. Furthermore, the EO demonstrated strong antioxidant activity, largely linked to carvacrol and oxygenated constituents. Chemical characterization by GC-MS, GC-FID and enantiomeric analysis strengthened the relationship between composition and bioactivity. Overall, L. origanoides EO emerged as a promising multifunctional natural product for therapeutic and cosmetic applications.