Modulation of Human Neutrophil Responses by the Essential Oils from Ferula akitschkensis and Their Constituents

J Agric Food Chem. 2016 Sep 28;64(38):7156-70. doi: 10.1021/acs.jafc.6b03205. Epub 2016 Sep 13.


Essential oils were obtained by hydrodistillation of the umbels+seeds and stems of Ferula akitschkensis (FAEOu/s and FAEOstm, respectively) and analyzed by gas chromatography and gas chromatography-mass spectrometry. Fifty-two compounds were identified in FAEOu/s; the primary components were sabinene, α-pinene, β-pinene, terpinen-4-ol, eremophilene, and 2-himachalen-7-ol, whereas the primary components of FAEOstm were myristicin and geranylacetone. FAEOu/s, β-pinene, sabinene, γ-terpinene, geranylacetone, isobornyl acetate, and (E)-2-nonenal stimulated [Ca(2+)]i mobilization in human neutrophils, with the most potent being geranylacetone (EC50 = 7.6 ± 1.9 μM) and isobornyl acetate 6.4 ± 1.7 (EC50 = 7.6 ± 1.9 μM). In addition, treatment of neutrophils with β-pinene, sabinene, γ-terpinene, geranylacetone, and isobornyl acetate desensitized the cells to N-formyl-Met-Leu-Phe (fMLF)- and interleukin-8 (IL-8)-induced [Ca(2+)]i flux and inhibited fMLF-induced chemotaxis. The effects of β-pinene, sabinene, γ-terpinene, geranylacetone, and isobornyl acetate on neutrophil [Ca(2+)]i flux were inhibited by transient receptor potential (TRP) channel blockers. Furthermore, the most potent compound, geranylacetone, activated Ca(2+) influx in TRPV1-transfected HEK293 cells. In contrast, myristicin inhibited neutrophil [Ca(2+)]i flux stimulated by fMLF and IL-8 and inhibited capsaicin-induced Ca(2+) influx in TRPV1-transfected HEK293 cells. These findings, as well as pharmacophore modeling of TRP agonists, suggest that geranylacetone is a TRPV1 agonist, whereas myristicin is a TRPV1 antagonist. Thus, at least part of the medicinal properties of Ferula essential oils may be due to modulatory effects on TRP channels.

Keywords: Ferula akitschkensis; calcium flux; essential oil; neutrophil; transient receptor potential channel.

MeSH terms

  • Aldehydes / pharmacology
  • Camphanes / pharmacology
  • Capsaicin / pharmacology
  • Cell Movement / drug effects
  • Ferula / chemistry*
  • Gas Chromatography-Mass Spectrometry
  • HEK293 Cells
  • HL-60 Cells
  • Humans
  • Immunologic Factors / pharmacology*
  • Interleukin-8 / metabolism
  • N-Formylmethionine Leucyl-Phenylalanine / analogs & derivatives
  • N-Formylmethionine Leucyl-Phenylalanine / metabolism
  • Neutrophils / drug effects*
  • Neutrophils / metabolism
  • Oils, Volatile / chemistry
  • Oils, Volatile / pharmacology*
  • Plant Oils / chemistry
  • Plant Oils / pharmacology*
  • Seeds / chemistry
  • TRPV Cation Channels / metabolism
  • Terpenes / pharmacology
  • Transient Receptor Potential Channels / metabolism


  • Aldehydes
  • Camphanes
  • Immunologic Factors
  • Interleukin-8
  • Oils, Volatile
  • Plant Oils
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Terpenes
  • Transient Receptor Potential Channels
  • 2-nonenal
  • pichtosin
  • N-Formylmethionine Leucyl-Phenylalanine
  • methionyl-leucyl-phenylalanine
  • geranylacetone
  • Capsaicin