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Planta Med 2015; 81(14): 1248-1254
DOI: 10.1055/s-0035-1546169
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Gamma-Terpinene Modulates Acute Inflammatory Response in Mice

Theresa Raquel de Oliveira Ramalho
1   Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Programa de Pós-Graduação em Biologia Celular e Molecular, João Pessoa, Paraíba, Brasil
,
Maria Talita Pacheco de Oliveira
1   Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Programa de Pós-Graduação em Biologia Celular e Molecular, João Pessoa, Paraíba, Brasil
,
Ana Luisa de Araujo Lima
2   Universidade Federal da Paraíba, Centro de Ciências da Saúde, Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, João Pessoa, Paraíba, Brasil
,
Claudio Roberto Bezerra-Santos
3   Universidade Federal da Paraíba, Departamento de Fisiologia e Patologia, Laboratório de Imunofarmacologia, João Pessoa, Paraíba, Brasil
,
Marcia Regina Piuvezam
1   Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Programa de Pós-Graduação em Biologia Celular e Molecular, João Pessoa, Paraíba, Brasil
2   Universidade Federal da Paraíba, Centro de Ciências da Saúde, Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, João Pessoa, Paraíba, Brasil
3   Universidade Federal da Paraíba, Departamento de Fisiologia e Patologia, Laboratório de Imunofarmacologia, João Pessoa, Paraíba, Brasil
› Author Affiliations
Further Information

Publication History

received 06 October 2014
revised 06 May 2015

accepted 07 May 2015

Publication Date:
01 July 2015 (online)

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Erratum for: Gamma-Terpinene Modulates Acute Inflammatory Response in MicePlanta Med 2015; 81(14): E3-E3
DOI: 10.1055/s-0035-1557790

Abstract

The monoterpene gamma-terpinene is a natural compound present in essential oils of a wide variety of plants, including the Eucalyptus genus, which has been reported to possess anti-inflammatory activity. The goal of this study was to evaluate the effect of gamma-terpinene on several in vivo experimental models of acute inflammation. Swiss mice were pretreated with gamma-terpinene and subjected to protocols of paw edema with different phlogistic agents such as carrageenan, prostaglandin-E2, histamine, or bradykinin. The microvascular permeability was measured by intraperitoneal injection of acetic acid and measuring the amount of protein extravasation. Carrageenan-induced peritonitis was used to analyze the effect of gamma-terpinene on inflammatory cell migration and cytokine production. We also developed an acute lung injury protocol to define the anti-inflammatory effect of gamma-terpinene. Mice pretreated with gamma-terpinene displayed reduced paw edema induced by carrageenan from 1–24 h after challenge. A similar reduction was observed when gamma-terpinene was administered after stimulation with PGE2, bradykinin, and histamine. Treatment with gamma-terpinene also inhibited fluid extravasation in the acetic acid model of microvascular permeability. In a carrageenan-induced peritonitis model, gamma-terpinene treatment reduced neutrophil migration as well as the production of interleukin-1β and tumor necrosis factor-α when compared to nontreated animals, and in the acute lung injury protocol, gamma-terpinene diminished the neutrophil migration into lung tissue independently of the total protein extravasation in the lung. These data demonstrate that, in different models of inflammation, treatment with gamma-terpinene alleviated inflammatory parameters such as edema and pro-inflammatory cytokine production, as well as cell migration into the inflamed site, and that this monoterpene has anti-inflammatory properties.

Key words

gamma-terpinene - mice - acute inflammation - mediators
 

  • References

  • 1 Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell 2010; 140: 771-776
    CrossrefPubMedGoogle Scholar
  • 2 Yang Y, Tang LO, Wei W. Prostanoids receptors signaling in different diseases/cancers progression. J Recept Signal Transduct Res 2013; 33: 14-27
    CrossrefPubMedGoogle Scholar
  • 3 Noursadeghi M, Cohen J. Immunopathogenesis of severe sepsis. J R Coll Physicians Lond 2000; 34: 432-436
    PubMedGoogle Scholar
  • 4 Hargreaves DC, Medzhitov R. Innate sensors of microbial infection. J Clin Immunol 2005; 25: 503-510
    CrossrefPubMedGoogle Scholar
  • 5 Filgueiras LR, Martins JO, Serezani CH, Capelozzi VL, Montes MBA, Jancar S. Sepsis-induced acute lung injury (ALI) is milder in diabetic rats and correlates with impaired NFkB activation. PLoS One 2012; 7: e44987
    CrossrefPubMedGoogle Scholar
  • 6 Yoshimura A, Suzuki M, Sakaguchi R, Hanada T, Yasukawa H. SOCS, inflammation, and autoimmunity. Front Immunol 2012; 3: 20
    PubMedGoogle Scholar
  • 7 Terpstra ML, Aman MD, Van Nieuw Amerongen GP, Groeneveld AB. Plasma biomarkers for acute respiratory distress syndrome: A systematic review and meta-analysis. Crit Care Med 2014; 42: 691-700
    CrossrefPubMedGoogle Scholar
  • 8 Johnson ER, Matthay MA. Acute lung injury: epidemiology, pathogenesis, and treatment. J Aerosol Med Pulm Drug Deliv 2010; 23: 243-252
    CrossrefPubMedGoogle Scholar
  • 9 Schimmer BP, Parker KL. Hormônio adrenocorticotrópico; esteroides adrenocorticais e seus análogos sintéticos; inibidores da síntese e das ações dos hormônios adrenocorticais. In: MGH, editor Goodman & Gilman: as bases farmacológicas da terapêutica. Rio de Janeiro: McGraw and Hill; 2003: 10
    Google Scholar
  • 10 Pereira NP, Miguel OG, Miguel MD. Composição química do óleo fixo obtido dos frutos secos da [Chamomilla recutita (L.) Rauschert] produzida no município de Mandirituba, PR. Rev Bras Farmacogn 2005; 15: 334-337
    CrossrefPubMedGoogle Scholar
  • 11 Zakaria ZA, Patahuddin H, Mohamad AS, Israf DA, Sulaiman MR. In vivo anti-nociceptive and anti-inflammatory activities of the aqueous extract of the leaves of Piper sarmentosum . J Ethnopharmacol 2010; 128: 42-48
    CrossrefPubMedGoogle Scholar
  • 12 Lima MS, Quintans-Junior LJ, Santana WAK, Martins Kaneto C, Pereira Soares MB, Villareal CF. Anti-inflammatory effects of carvacrol: Evidence for a key role of interleukin-10. Eur J Pharmacol 2013; 14: 112-117
    PubMedGoogle Scholar
  • 13 Guimarães AG, Quintans JS, Quintans-Junior LJ. Monoterpenes with analgesic activity – a systematic review. Phytother Res 2013; 27: 1-15
    CrossrefPubMedGoogle Scholar
  • 14 Siveen KS, Kuttan G. Thujone inhibits lung metastasis induced by B16F-10 melanoma cells in C57BL/6 mice. Can J Physiol Pharmacol 2011; 89: 691-703
    CrossrefPubMedGoogle Scholar
  • 15 Chagas ACS, Passos WM, Prates HT, Leite RM, Furlong J, Pereira Fortes IC. Acaricide effect of Eucalyptus spp. essential oils and concentrated emulsion on Boophilus microplus . Braz J Vet Res Anim Sci 2002; 39: 247-253
    PubMedGoogle Scholar
  • 16 Kim KN, Ko YJ, Yang HM, Ham YM, Roh SW, Jeon YJ, Ahn G, Kang MC, Yoon WJ, Kim D, Oda T. Anti-inflammatory effect of essential oil and its constituents from fingered citron (Citrus medica L. var. sarcodactylis) through blocking JNK, ERK and NF-κB signaling pathways in LPS-activated RAW 264.7 cells. Food Chem Toxicol 2013; 57: 126-131
    CrossrefPubMedGoogle Scholar
  • 17 Béjaoui A, Chaabane H, Jemli M, Boulila A, Boussaid M. Essential oil composition and antibacterial activity of Origanum vulgare subsp. glandulosum Desf. at different phenological stages. J Med Food 2013; 16: 1115-1120
    CrossrefPubMedGoogle Scholar
  • 18 Tao N, Jia L, Zhou H. Anti-fungal activity of Citrus reticulata Blanco essential oil against Penicillium italicum and Penicillium digitatum . Food Chem 2014; 153: 265-272
    CrossrefPubMedGoogle Scholar
  • 19 Öztürk M. Anticholinesterase and antioxidant activities of Savoury (Satureja thymbra L.) with identified major terpenes of the essential oil. Food Chem 2012; 134: 48-54
    CrossrefPubMedGoogle Scholar
  • 20 Milde J, Elstner EF, Grassmann J. Synergistic inhibition of low-density lipoprotein oxidation by rutin, γ-terpinene, and ascorbic acid. Phytomedicine 2004; 11: 105-113
    CrossrefPubMedGoogle Scholar
  • 21 Damas J, Remacle-Volon G. Influence of a long-acting bradykinin antagonist, Hoe 140, on some acute inflammatory reactions in the rat. Eur J Pharmacol 1992; 211: 81-86
    CrossrefPubMedGoogle Scholar
  • 22 Handy RL, Moore PK. A comparison of the effects of L-NAME, 7-NI and L-NIL on carrageenan-induced hindpaw oedema and NOS activity. Br J Pharmacol 1998; 123: 1119-1126
    CrossrefPubMedGoogle Scholar
  • 23 Medeiros MV, Binhara IM, Moreno H, Zats R, De Nucci G, Antunes E. Effect of chronic nitric oxide synthesis inhibition on the inflammatory responses induced by carrageenan in rats. Eur J Pharmacol 1995; 285: 109-114
    CrossrefPubMedGoogle Scholar
  • 24 Vaz ZR, Cechinel V, Yunes RA, Calixto JB. Antinociceptive action of 2-(-4bromobenzoyl)-3-methy-4–6-dimethoxybenzofuran, a novel xanthoxyline derivative of chemical and thermal models of nociception in mice. J Pharmacol Exp Ther 1996; 278: 304-312
    PubMedGoogle Scholar
  • 25 Hajhashemi V, Sajjadj SE, Zomorodkia M. Antinociceptive and anti-inflammatory activities of Bunium persicum essential oil, hydroalcoholic and polyphenolic extracts in animal models. Pharm Biol 2011; 49: 146-151
    CrossrefPubMedGoogle Scholar
  • 26 Claudino RF, Kassuya CAL, Ferreira J, Calixto JB. Pharmacological and molecular characterization of the mechanisms involved in prostaglandin E2-induced mouse paw edema. J Pharmacol Exp Ther 2006; 318: 611-618
    CrossrefPubMedGoogle Scholar
  • 27 Morimoto K, Shirata N, Taketomi Y, Tsuchiya S, Segi-Nishida E, Inazumi T, Kabashima K, Tanaka S, Murakami M, Narumiya S, Sugimoto Y. Prostaglandin E2-EP3 signaling induces inflammatory swelling by mast cell activation. J Immunol 2014; 192: 1130-1137
    CrossrefPubMedGoogle Scholar
  • 28 Trabold R, Eros C, Zweckberger K, Relton H, Nussberger J, Müller-Esterl W, Bader M, Whalley E, Plesnila N. The role of bradykinin B(1) and B(2) receptors for secondary brain damage after traumatic brain injury in mice. J Cereb Blood Flow Metab 2010; 30: 130-139
    CrossrefPubMedGoogle Scholar
  • 29 Falhout M, Deraedt R, Jougney S, Delevalcee F. Release of prostaglandin E and F in an algogenic reaction and its inhibition. Eur J Pharmacol 1980; 51: 17-24
    PubMedGoogle Scholar
  • 30 Collier HO, Dinneen LC, Johnson CA, Schneider C. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol Chemother 1968; 32: 295-310
    CrossrefPubMedGoogle Scholar
  • 31 Deraedt R, Jougney S, Delevalcee F, Flahaut M. Release of prostaglandin E and F in an algogenic reaction and its inhibition. Eur J Pharmacol 1980; 51: 17-24
    PubMedGoogle Scholar
  • 32 Malech HL, Gallin JI. Current concepts: immunology-neutrophils in human diseases. N Engl J Med 1987; 317: 687-694
    CrossrefPubMedGoogle Scholar
  • 33 Salvemini D, Mazzon E, Dugo L, Riley DP, Serraino I, Caputi AP, Cuzzocrea S. Pharmacological manipulation of the inflammatory cascade by superoxide dismutase mimetic. Br J Pharmacol 2001; 132: 815-827
    CrossrefPubMedGoogle Scholar
  • 34 Loram LC, Fuller A, Fick LG, Cartmell T, Poole S, Mitchell D. Cytokine profiles during carrageenan-induced inflammatory hyperalgesia in rat muscle and hind paw. J Pain 2007; 8: 127-136
    CrossrefPubMedGoogle Scholar
  • 35 Omote K, Hazama K, Kawamata T, Kawamata M, Nakayaka Y, Toriyabe M, Namiki A. Peripheral nitric oxide in carrageenan-induced inflammation. Brain Res 2001; 912: 171-175
    CrossrefPubMedGoogle Scholar
  • 36 Juergens UR, Stober M, Vetter H. Inhibition of cytokine production and arachidonic acid metabolism by eucalyptol (1, 8-cineole) in human blood monocytes in vitro . Eur J Med Res 1998; 17: 508-510
    PubMedGoogle Scholar
  • 37 Hirahara K, Poholek A, Vahedi G, Laurence A, Kanno Y, Milner JD, OʼShea JJ. Mechanisms underlying helper T-cell plasticity: Implications for immune-mediated disease. J Allergy Clin Immunol 2013; 131: 1276-1287
    CrossrefPubMedGoogle Scholar