Gamma-Terpinene Modulates Acute Inflammatory Response in Mice

Planta Med. 2015 Sep;81(14):1248-54. doi: 10.1055/s-0035-1546169. Epub 2015 Jul 1.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Carrageenan / toxicity
  • Cyclohexane Monoterpenes
  • Cytokines / metabolism
  • Dinoprostone / toxicity
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Edema / chemically induced
  • Edema / drug therapy
  • Female
  • Histamine / pharmacology
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation / pathology
  • Lipopolysaccharides / toxicity
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Monoterpenes / administration & dosage
  • Monoterpenes / pharmacology*
  • Peritonitis / chemically induced
  • Peritonitis / drug therapy
  • Peritonitis / pathology

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclohexane Monoterpenes
  • Cytokines
  • Lipopolysaccharides
  • Monoterpenes
  • gamma-terpinene
  • Histamine
  • Carrageenan
  • Dinoprostone