Myristicin from Athamanta sicula L.: A Potential Natural Antimicrobial Agent

<i>Athamanta</i> L. is a small genus of the Apiaceae family, comprising only sixteen species and subspecies, which are distributed in the Canary Islands, Central Europe, and the Mediterranean basin. <b>Background/Objectives</b>: Since the time of Dioscurides, the species of this genus have been reported to have had several ethnopharmacological activities, and some of them are also used currently. <i>Athamanta sicula</i> L., growing in Italy, Tunisia, Algeria, and Morocco, is the only species of this genus present in Sicily. To further explore the phytochemical profile and biological properties of this species, the present study focused on the essential oil (EO) extracted from the aerial parts of wild <i>A. sicula</i> populations collected in central Sicily. <b>Methods</b>: The chemical composition of the EO, obtained by hydrodistillation, was determined by GC-MS analysis. The presence of myristicin was confirmed by isolation and by ¹H-NMR spectroscopic characterization. <b>Results</b>: The EO and its main constituents have been tested for possible antimicrobial properties against several bacterial strains, showing MIC values in the of 15-30 mg/mL range, and the mechanism of action was further investigated, revealing membrane-targeting effects consistent with outer membrane permeabilization. In addition, antibiofilm activity (with up to ~80% inhibition of biofilm formation at sub-MICs), antioxidant potential (demonstrating dose-dependent radical scavenging activity), and biocompatibility with eukaryotic cells were assessed to provide a comprehensive pharmacological profile of <i>A. sicula</i> EO. Specifically, the most abundant constituent was myristicin (62.2%), the principal representative of the phenylpropanoid class (64.4%). Hydrocarbon monoterpenes represented the second class of the EO (27.4%), with <i>β</i>-phellandrene (12.2%) as the main compound. <b>Conclusions</b>: Myristicin emerged as the key contributor to the antimicrobial and antibiofilm activity of the EO. The obtained results highlight the relevance of <i>A. sicula</i> EO as a myristicin-rich essential oil with notable in vitro biological activity.