Neutrophil Immunomodulatory Activity of Farnesene, a Component of <i>Artemisia</i> <i>dracunculus</i> Essential Oils

oleh: Igor A. Schepetkin, Gulmira Özek, Temel Özek, Liliya N. Kirpotina, Andrei I. Khlebnikov, Robyn A. Klein, Mark T. Quinn

Format: Article
Diterbitkan: MDPI AG 2022-05-01

Deskripsi

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 Ca<sup>2+</sup> 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 A<sub>4</sub>, inhibited Ca<sup>2+</sup> influx induced in human neutrophils by <i>f</i>MLF (IC<sub>50</sub> = 1.2 μM), WKYMVM (IC<sub>50</sub> = 1.4 μM), or interleukin 8 (IC<sub>50</sub> = 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.