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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.

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Our data show the anti-allergic and immunoregulatory properties of C. sympodialis, acting mostly through the active compound warifteine, to inhibit the airway hyperreactivity and lung remodeling through a mechanism at least partially dependent of IL-13 and eosinophil inhibition. Therefore placing warifteine as an interesting therapeutic candidate in allergic inflammation and corroborating the folk medicine use of C. sympodialis as anti-allergic plant.

Gamma-terpinene is a monoterpene present in the essential oils of several plants, including those from the genus. This molecule was recently described as anti-inflammatory and microbiocidal, but little is known about the mechanisms behind its effects. The aim of the present study was to investigate the effect of gamma-terpinene on the lipopolysaccharide-induced production of cytokines by murine peritoneal macrophages. Gamma-terpinene treatment was found to reduce the production of proinflammatory cytokines, such as interleukin-1 and interleukin-6, and enhance that of the anti-inflammatory cytokine interleukin-10. This was accompanied by increased levels of the enzyme cycloxygenase-2 and its product, the lipid mediator prostaglandin E. Inhibition of cycloxygenase-2 with nimesulide abolished the potentiating effect of gamma-terpinene on interleukin-10 production. Moreover, nimesulide treatment also abrogated the inhibitory effect of gamma-terpinene on interleukin-1 and interleukin-6. Furthermore, in macrophages from mice deficient in the interleukin-10 gene, gamma-terpinene failed to inhibit interleukin-1 and interleukin-6 production. These results suggest that this monoterpene promotes the prostaglandin E/interleukin-10 axis, which inhibits the production of these proinflammatory cytokines.

The murine model of OVA-induced immediate allergic reaction was used to evaluate the effectiveness of intraperitoneal sub-acute treatment with the leaf hydroalcoholic extract of Cissampelos sympodialis (AFL) in the anaphylactic shock reaction, IgE production and the background proliferative response. BALB/c mice treated with AFL ranging from 200 to 400 mg/kg/day for 5 days before and during OVA-sensitization strongly reduced the animal death and promoted reduction in total and OVA-specifi c serum IgE level. Spleen cells from AFL-treated sensitized animals showed a decreased proliferative background response when compared with non-sensitized animals. These results demonstrated that sub-acute intraperitoneal treatment with Cissampelos sympodialis extract has an anti-allergic effect.

Cissampelos sympodialis Eichl. (Menispermaceae) root infusion is used in Northeast Brazil to treat allergic asthma. We have previously shown that oral use of the plant extract reduces eosinophil infiltration into the lung of ovalbumin (OVA)- sensitized mice. However, drugs taken by inhalation route to treat asthma achieve better outcomes. Thereby, in this study, we evaluated the inhaled C. sympodialis alcoholic extract as a therapeutic treatment in OVA-sensitized BALB/c mice. The parameters which were analyzed consisted of leukocyte recruitment to the airway cavity, tissue remodeling and cell profile. The inhaled extract inhibited mainly eosinophil recruitment to the pleural cavity, bronchoalveolar lavage and peripheral blood. This treatment reduced the OVA-specific IgE serum titer and leukocyte infiltration in the peribronchiolar and pulmonary perivascular areas as well as mucus production. In addition, we also tested isolated alkaloids from the plant extract. The flow cytometric analysis showed that methylwarifteine (MW) and, mainly, the inhaled extract reduced the number of CD3+T cells and eosinophil-like cells. Therefore, inhaled C. sympodialis extract and MW lead to down-regulation of inflammatory cell infiltration with remarkable decrease in the number of T cells in an experimental model of respiratory allergy, suggesting that the plant can be delivered via inhalation route to treat allergic asthma.