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

Igor A. Schepetkin, Svetlana V. Kushnarenko, Gulmira Özek, Liliya N. Kirpotina, Pritam Sinharoy, Gulzhakhan A. Utegenova, Karime T. Abidkulova, Temel Özek, Kemal Hüsnü Can Başer, Anastasia R. Kovrizhina, Andrey Ivanovich Khlebnikov, Derek S. Damron, Mark T. Quinn

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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, Î3-terpinene, geranylacetone, isobornyl acetate, and (E)-2-nonenal stimulated [Ca2+]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, Î3-terpinene, geranylacetone, and isobornyl acetate desensitized the cells to N-formyl-Met-Leu-Phe (fMLF)- and interleukin-8 (IL-8)-induced [Ca2+]i flux and inhibited fMLF-induced chemotaxis. The effects of β-pinene, sabinene, Î3-terpinene, geranylacetone, and isobornyl acetate on neutrophil [Ca2+]i flux were inhibited by transient receptor potential (TRP) channel blockers. Furthermore, the most potent compound, geranylacetone, activated Ca2+ influx in TRPV1-transfected HEK293 cells. In contrast, myristicin inhibited neutrophil [Ca2+]i flux stimulated by fMLF and IL-8 and inhibited capsaicin-induced Ca2+ 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.

Original languageEnglish
Pages (from-to)7156-7170
Number of pages15
JournalJournal of Agricultural and Food Chemistry
Issue number38
Publication statusPublished - 28 Sep 2016
Externally publishedYes



  • calcium flux
  • essential oil
  • Ferula akitschkensis
  • neutrophil
  • transient receptor potential channel

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

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