Bioactive potential of Ecuadorian Lippia dulcis essential oil: accelerated wound healing and chemical profiling

This study describes the results of a phytochemical and pharmacological study of Lippia dulcis Trevir, grown in southern Ecuador, where the plant, commonly known by the name buscapina, is widely used by the local population for its therapeutic properties in the treatment of gastrointestinal disorders, mainly colic and spasms. Steam distillation of the aerial parts afforded an essential oil (EO) characterized by GC-MS/FID as a sesquiterpene-rich chemotype (96.89%). β-caryophyllene (18.89%), δ-selinene (11.78%), δ-cadinene (11.07%), β-cubebene (10.51%), and bicyclogermacrene (8.14%) were the predominant constituents of the oil. On the contrary, the hydrolate resulting from the distillation mainly contained oxygenated degradation products of the intensely sweet chemical hernandulcin and was biologically inert. Functional assessment using NIH/3T3 fibroblasts revealed a concentration-time dependent biphasic response. At 0.5-0.75 μL/mL and ≤ 6 h exposure, the EO significantly accelerated wound closure in scratch assays without compromising cell membrane integrity, while simultaneously inducing a moderate increase in intracellular reactive oxygen species (ROS) (6.9-11.0 times compared to the control). Prolonged exposure (24 h) to concentrations ≥ 0.5 μL/mL of the EO led to marked cytotoxicity (IC₅₀ = 0.45 μL/mL), characterized by metabolic impairment, membrane destruction, and massive oxidative stress (30 times increase in intracellular ROS compared to the control). In conclusion, the EO of L. dulcis from southern Ecuador exhibits a potential therapeutic window separating pro-migratory effects on fibroblasts from cytotoxic activity.