title: Gamma-Terpinene Modulates Acute Inflammatory Response in Mice.
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.
authors.affiliation: Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Programa de Pós-Graduação em Biologia Celular e Molecular, João Pessoa, Paraíba, Brasil.
authors.forename: Theresa Raquel de Oliveira
authors.initials: TR
authors.lastname: Ramalho
authors.affiliation: Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Programa de Pós-Graduação em Biologia Celular e Molecular, João Pessoa, Paraíba, Brasil.
authors.forename: Maria Talita Pacheco de
authors.initials: MT
authors.lastname: Oliveira
authors.affiliation: Universidade Federal da Paraíba, Centro de Ciências da Saúde, Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, João Pessoa, Paraíba, Brasil.
authors.forename: Ana Luisa de Araujo
authors.initials: AL
authors.lastname: Lima
authors.affiliation: Universidade Federal da Paraíba, Departamento de Fisiologia e Patologia, Laboratório de Imunofarmacologia, João Pessoa, Paraíba, Brasil.
authors.forename: Claudio Roberto
authors.initials: CR
authors.lastname: Bezerra-Santos
authors.affiliation: Universidade Federal da Paraíba, Centro de Ciências Exatas e da Natureza, Programa de Pós-Graduação em Biologia Celular e Molecular, João Pessoa, Paraíba, Brasil.
authors.forename: Marcia Regina
authors.initials: MR
authors.lastname: Piuvezam
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002351:Carrageenan / Q000633:toxicity; D000081005:Cyclohexane Monoterpenes; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006632:Histamine / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D010538:Peritonitis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000081005:Cyclohexane Monoterpenes; D016207:Cytokines; D008070:Lipopolysaccharides; D039821:Monoterpenes; C018669:gamma-terpinene; D006632:Histamine; D002351:Carrageenan; D015232:Dinoprostone