Inhibition of Human Neutrophil Responses by the Essential Oil of Artemisia kotuchovii and Its Constituents

Essential oils were obtained by hydrodistillation of the flowers+leaves and stems of Artemisia kotuchovii Kupr. (AKEO(f+l) and AKEO(stm), respectively) and analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The primary components of the oils were estragole, (E)- and (Z)-β-ocimenes, methyleugenol, limonene, spathulenol, β-pinene, myrcene, and (E)-methyl cinnamate. Seventy-four constituents were present at concentrations from 0.1 to 1.0%, and 34 compounds were identified in trace (<0.1%) amounts in one or both plant components. Screening of the essential oils for biological activity showed that AKEO(stm), but not AKEOf+l, inhibited N-formyl-Met-Leu-Phe (fMLF)-stimulated Ca(2+) flux and chemotaxis and phorbol-12-myristate-13-acetate (PMA)-induced reactive oxygen species (ROS) production in human neutrophils. Selected pure constituents, representing >96% of the AKEO(stm) composition, were also tested in human neutrophils and HL-60 cells transfected with N-formyl peptide receptor 1 (FPR1). One component, 6-methyl-3,5-heptadien-2-one (MHDO), inhibited fMLF- and interleukin 8 (IL-8)-stimulated Ca(2+) flux, fMLF-induced chemotaxis, and PMA-induced ROS production in human neutrophils. MHDO also inhibited fMLF-induced Ca(2+) flux in FPR1-HL60 cells. These results suggest that MHDO may be effective in modulating some innate immune responses, possibly by inhibition of neutrophil migration and ROS production.