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

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Schepetkin I. A., Kushnarenko S. V., ÖZEK G., Kirpotina L. N., Sinharoy P., Utegenova G. A., ...More

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol.64, no.38, pp.7156-7170, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 64 Issue: 38
  • Publication Date: 2016
  • Doi Number: 10.1021/acs.jafc.6b03205
  • Journal Name: JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.7156-7170
  • Keywords: Ferula akitschkensis, calcium flux, essential oil, neutrophil, transient receptor potential channel, SUBSTANTIA-GELATINOSA NEURONS, PHOSPHOLIPASE-C ACTIVITY, FORMYL PEPTIDE RECEPTOR, ANTIMICROBIAL ACTIVITIES, CHEMICAL-COMPOSITION, MYRISTICA-FRAGRANS, ACTIVE PRINCIPLES, CATION CHANNEL, TRPV1 CHANNELS, CALCIUM
  • Anadolu University Affiliated: Yes

Abstract

Essential oils were obtained by hydrodistillation of the umbels+seeds and stems of Ferula akitschkensis (FAEO(u/s) and FAEO(stm), respectively) and analyzed by gas chromatography and gas chromatography-mass spectrometry. Fifty-two compounds were identified in FASO(u/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. FAEO(u/s), beta-pinene, sabinene, gamma-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 mu M) and isobornyl acetate 6.4 +/- 1.7 (EC50 = 7.6 +/- 1.9 mu M). 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 [Ca2+](i) flux and inhibited fMLF-induced chemotaxis. The effects of beta-pinene, sabinene, gamma-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.