title: Modulation of Human Neutrophil Responses by the Essential Oils from Ferula akitschkensis and Their Constituents.
abstract: 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.
authors: Department of Microbiology and Immunology, Montana State University , Bozeman, Montana 59717, United States.
authors: Igor A
authors: IA
authors: Schepetkin
authors: Institute of Plant Biology and Biotechnology , Almaty 050040, Republic of Kazakhstan.
authors: Svetlana V
authors: SV
authors: Kushnarenko
authors: Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University , Eskisehir 26470, Turkey.
authors: Gulmira
authors: G
authors: Özek
authors: Department of Microbiology and Immunology, Montana State University , Bozeman, Montana 59717, United States.
authors: Liliya N
authors: LN
authors: Kirpotina
authors: Department of Biological Sciences, Kent State University , Kent, Ohio 44242, United States.
authors: Pritam
authors: P
authors: Sinharoy
authors: Institute of Plant Biology and Biotechnology , Almaty 050040, Republic of Kazakhstan.|Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University , Almaty 050040, Republic of Kazakhstan.
authors: Gulzhakhan A
authors: GA
authors: Utegenova
authors: Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University , Almaty 050040, Republic of Kazakhstan.
authors: Karime T
authors: KT
authors: Abidkulova
authors: Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University , Eskisehir 26470, Turkey.
authors: Temel
authors: T
authors: Özek
authors: Department of Pharmacognosy, Faculty of Pharmacy, Near East University , Nicosia, North Cyprus.
authors: Kemal Hüsnü Can
authors: KH
authors: Başer
authors: Department of Biotechnology and Organic Chemistry, Tomsk Polytechnic University , Tomsk 634050, Russia.
authors: Anastasia R
authors: AR
authors: Kovrizhina
authors: Department of Biotechnology and Organic Chemistry, Tomsk Polytechnic University , Tomsk 634050, Russia.|Department of Chemistry, Altai State Technical University , Barnaul 656038, Russia.
authors: Andrei I
authors: AI
authors: Khlebnikov
authors: Department of Biological Sciences, Kent State University , Kent, Ohio 44242, United States.
authors: Derek S
authors: DS
authors: Damron
authors: Department of Microbiology and Immunology, Montana State University , Bozeman, Montana 59717, United States.
authors: Mark T
authors: MT
authors: Quinn
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D001892:Camphanes / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D005309:Ferula / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D057809:HEK293 Cells; D018922:HL-60 Cells; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D016209:Interleukin-8 / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000031:analogs & derivatives / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009822:Oils, Volatile / Q000737:chemistry / Q000494:pharmacology*; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry; D050916:TRPV Cation Channels / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology; D050051:Transient Receptor Potential Channels / Q000378:metabolism
chemical_list: D000447:Aldehydes; D001892:Camphanes; D007155:Immunologic Factors; D016209:Interleukin-8; D009822:Oils, Volatile; D010938:Plant Oils; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D013729:Terpenes; D050051:Transient Receptor Potential Channels; C013166:2-nonenal; C011331:pichtosin; D009240:N-Formylmethionine Leucyl-Phenylalanine; C042205:methionyl-leucyl-phenylalanine; C009884:geranylacetone; D002211:Capsaicin
keywords: Ferula akitschkensis; calcium flux; essential oil; neutrophil; transient receptor potential channel