Neutrophil Immunomodulatory Activity of Farnesene, a Component of Artemisia dracunculus Essential Oils

Despite their reported therapeutic properties, not much is known about the immunomodulatory activity of essential oils present in Artemisia species. We isolated essential oils from the flowers and leaves of five Artemisia species: A. tridentata, A. ludoviciana, A. dracunculus, A. frigida, and A. cana. The chemical composition of the Artemisia essential oil samples had similarities and differences as compared to those previously reported in the literature. The main components of essential oils obtained from A. tridentata, A. ludoviciana, A. frigida, and A. cana were camphor (23.0-51.3%), 1,8-cineole (5.7-30.0%), camphene (1.6-7.7%), borneol (2.3-14.6%), artemisiole (1.2-7.5%), terpinen-4-ol (2.0-6.9%), alpha-pinene (0.8-3.9%), and santolinatriene (0.7-3.5%). Essential oils from A. dracunculus were enriched in methyl chavicol (38.8-42.9%), methyl eugenol (26.1-26.4%), terpinolene (5.5-8.8%), (E/Z)-beta-ocimene (7.3-16.0%), beta-phellandrene (1.3-2.2%), p-cymen-8-ol (0.9-2.3%), and xanthoxylin (1.2-2.2%). A comparison across species also demonstrated that some compounds were present in only one Artemisia species. Although Artemisia essential oils were weak activators of human neutrophils, they were relatively more potent in inhibiting subsequent neutrophil Ca2+ mobilization with N-formyl peptide receptor 1 (FPR1) agonistf MLF- and FPR2 agonist WKYMVM, with the most potent being essential oils from A. dracunculus. Further analysis of unique compounds found in A. dracunculus showed that farnesene, a compound with a similar hydrocarbon structure as lipoxin A(4), inhibited Ca2+ influx induced in human neutrophils by fMLF (IC50 = 1.2 mu M), WKYMVM (IC50 = 1.4 mu M), or interleukin 8 (IC50 = 2.6 mu M). Pretreatment with A. dracunculus essential oils and farnesene also inhibited human neutrophil chemotaxis induced byfMLF, suggesting these treatments down-regulated human neutrophil responses to inflammatory chemoattractants. Thus, our studies have identified farnesene as a potential anti-inflammatory modulator of human neutrophils.