TY - JOUR
T1 - Modulation of Human Neutrophil Responses by the Essential Oils from Ferula akitschkensis and Their Constituents
AU - Schepetkin, Igor A.
AU - Kushnarenko, Svetlana V.
AU - Özek, Gulmira
AU - Kirpotina, Liliya N.
AU - Sinharoy, Pritam
AU - Utegenova, Gulzhakhan A.
AU - Abidkulova, Karime T.
AU - Özek, Temel
AU - Başer, Kemal Hüsnü Can
AU - Kovrizhina, Anastasia R.
AU - Khlebnikov, Andrey Ivanovich
AU - Damron, Derek S.
AU - Quinn, Mark T.
PY - 2016/9/28
Y1 - 2016/9/28
N2 - 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.
AB - 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.
KW - calcium flux
KW - essential oil
KW - Ferula akitschkensis
KW - neutrophil
KW - transient receptor potential channel
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U2 - 10.1021/acs.jafc.6b03205
DO - 10.1021/acs.jafc.6b03205
M3 - Article
AN - SCOPUS:84989261252
VL - 64
SP - 7156
EP - 7170
JO - Journal of Agricultural and Food Chemistry
JF - Journal of Agricultural and Food Chemistry
SN - 0021-8561
IS - 38
ER -