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

• DOI: 10.1021/acs.jafc.6b03205
• Publication Date: 2016-09-02T10:10:42Z
• Authors: Igor A. Schepetkin; Svetlana V. Kushn...; Gulmira Özek; Liliya N. Kirpotina; Pritam Sinharoy; Gulzhakhan A. Ute...; Karime T. Abidkulova; Temel Özek; Kemal Hüsnü Can B...; Anastasia R. Kovr...; Andrei I. Khlebnikov; Derek S. Damron; Mark T. Quinn
• Keywords: 0301 basic medicine; Neutrophils; TRPV Cation Channels; HL-60 Cells; Gas Chromatography-Mass Spectrometry; 03 medical and health sciences; Transient Receptor Potential Channels; Cell Movement; Oils, Volatile; Transient Receptor Potential Channel; Humans; Immunologic Factors; Plant Oils; Aldehydes; Calcium Flux; Camphanes; Terpenes; Neutrophil; Interleukin-8; Ferula Akitschkensis; Essential Oil; Ferula; 3. Good health; N-Formylmethionine Leucyl-Phenylalanine; HEK293 Cells; Seeds; Capsaicin

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.