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J Agric Food Chem

Title:		Modulation of Human Neutrophil Responses by the Essential Oils from Ferula akitschkensis and Their Constituents
Author(s):		Schepetkin IA; Kushnarenko SV; Ozek G; Kirpotina LN; Sinharoy P; Utegenova GA; Abidkulova KT; Ozek T; Baser KH; Kovrizhina AR; Khlebnikov AI; Damron DS; Quinn MT;
Address:		"Department of Microbiology and Immunology, Montana State University , Bozeman, Montana 59717, United States. Institute of Plant Biology and Biotechnology , Almaty 050040, Republic of Kazakhstan. Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University , Eskisehir 26470, Turkey. Department of Biological Sciences, Kent State University , Kent, Ohio 44242, United States. Faculty of Biology and Biotechnology, Al-Farabi Kazakh National University , Almaty 050040, Republic of Kazakhstan. Department of Pharmacognosy, Faculty of Pharmacy, Near East University , Nicosia, North Cyprus. Department of Biotechnology and Organic Chemistry, Tomsk Polytechnic University , Tomsk 634050, Russia. Department of Chemistry, Altai State Technical University , Barnaul 656038, Russia"
Journal Title:		J Agric Food Chem
Year:		2016
Volume:		20160913
Issue:		38
Page Number:		7156 - 7170
DOI:		10.1021/acs.jafc.6b03205
ISSN/ISBN:		1520-5118 (Electronic) 0021-8561 (Print) 0021-8561 (Linking)
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, alpha-pinene, beta-pinene, terpinen-4-ol, eremophilene, and 2-himachalen-7-ol, whereas the primary components of FAEOstm were myristicin and geranylacetone. FAEOu/s, beta-pinene, sabinene, gamma-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 muM) and isobornyl acetate 6.4 +/- 1.7 (EC50 = 7.6 +/- 1.9 muM). In addition, treatment of neutrophils with beta-pinene, sabinene, gamma-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 beta-pinene, sabinene, gamma-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:		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-Formylmethi;
Notes:		"MedlineSchepetkin, Igor A Kushnarenko, Svetlana V Ozek, Gulmira Kirpotina, Liliya N Sinharoy, Pritam Utegenova, Gulzhakhan A Abidkulova, Karime T Ozek, Temel Baser, Kemal Husnu Can Kovrizhina, Anastasia R Khlebnikov, Andrei I Damron, Derek S Quinn, Mark T eng P30 GM110732/GM/NIGMS NIH HHS/ 2016/09/03 J Agric Food Chem. 2016 Sep 28; 64(38):7156-70. doi: 10.1021/acs.jafc.6b03205. Epub 2016 Sep 13"