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

Abstract

Despite their reported therapeutic properties, not much is known about the immunomodulatory activity of essential oils present in <i>Artemisia</i> species. We isolated essential oils from the flowers and leaves of five <i>Artemisia</i> species: <i>A. tridentata</i>, <i>A. ludoviciana</i>, <i>A. dracunculus</i>, <i>A. frigida</i>, and <i>A. cana</i>. The chemical composition of the <i>Artemisia</i> essential oil samples had similarities and differences as compared to those previously reported in the literature. The main components of essential oils obtained from <i>A. tridentata</i>, <i>A. ludoviciana</i>, <i>A. frigida</i>, and <i>A. cana</i> 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%), α-pinene (0.8-3.9%), and santolinatriene (0.7-3.5%). Essential oils from <i>A. dracunculus</i> were enriched in methyl chavicol (38.8-42.9%), methyl eugenol (26.1-26.4%), terpinolene (5.5-8.8%), (<i>E</i>/<i>Z</i>)-β-ocimene (7.3-16.0%), β-phellandrene (1.3-2.2%), <i>p</i>-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 <i>Artemisia</i> species. Although <i>Artemisia</i> essential oils were weak activators of human neutrophils, they were relatively more potent in inhibiting subsequent neutrophil Ca²⁺ mobilization with <i>N</i>-formyl peptide receptor 1 (FPR1) agonist <i>f</i>MLF- and FPR2 agonist WKYMVM, with the most potent being essential oils from <i>A. dracunculus</i>. Further analysis of unique compounds found in <i>A. dracunculus</i> showed that farnesene, a compound with a similar hydrocarbon structure as lipoxin A₄, inhibited Ca²⁺ influx induced in human neutrophils by <i>f</i>MLF (IC₅₀ = 1.2 μM), WKYMVM (IC₅₀ = 1.4 μM), or interleukin 8 (IC₅₀ = 2.6 μM). Pretreatment with <i>A. dracunculus</i> essential oils and farnesene also inhibited human neutrophil chemotaxis induced by <i>f</i>MLF, 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.