Inhaled Cissampelos sympodialis down-regulates airway allergic reaction by reducing lung CD3+ T cells.

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.

Anti-allergic properties of Cissampelos sympodialis and its isolated alkaloid warifteine.

Development of new agents capable of regulating eosinophilic inflammation can uncover novel therapeutic approaches for the treatment of allergic diseases, such as asthma. Here, we evaluated the anti-allergic properties of an extract of the Brazilian Menispermaceae Cissampelos sympodialis, focusing on its effects on allergic eosinophilia. By studying two models of allergic inflammation, an asthma model and the allergic pleurisy in actively sensitized Balb/c mice, we observed that the oral pre-treatment with C. sympodialis reduced pleural eosinophil influx triggered by allergen challenge in a dose-dependent manner. The mechanism involved in C. sympodialis inhibitory effect appeared to be independent of a direct effect on eosinophil locomotory machinery, but depend on a blockage of eotaxin production, a key eosinophil chemoattractant with important roles in allergic reactions. C. sympodialis was also able to affect eosinophil activation, as attested by its ability of inhibiting formation of new cytoplasmic lipid bodies and the secretion of cysteinyl leukotrienes. The alkaloid warifteine isolated from the C. sympodialis extract represents an active component responsible for the anti-eosinophilic effects of the extract, since warifteine was able to reproduce C. sympodialis inhibitory effects on allergic eosinophilia and cysteinyl leukotrienes production. Of interest, C. sympodialis and warifteine post-treatments also effectively inhibited eosinophilic reaction observed after allergic challenge. Therefore, C. sympodialis/warifteine may be a promising anti-allergic therapy, inasmuch as it presents potent anti-eosinophil and anti-leukotrienes activities.

Effectiveness of Cissampelos sympodialis and its isolated alkaloid warifteine in airway hyperreactivity and lung remodeling in a mouse model of asthma.

BACKGROUND: Cissampelos sympodialis Eichl. (Menispermaceae) is a plant found in Northeastern and Southeast of Brazil and hot water infusion of C. sympodialis root bark is largely used in the indigenous and folk medicine to treat several inflammatory disorders, including asthma. Asthma is a chronic inflammatory allergic disease characterized by airway hyperreactivity (AHR), eosinophil tissue infiltration and lung remodeling. The aim of this study was to evaluate the therapeutic effect of C. sympodialis and its isolated alkaloid warifteine on allergen triggered airway hyperreactivity (AHR) and lung remodeling in murine model of asthma. METHODOLOGY/PRINCIPAL FINDINGS: The oral pre-treatment with C. sympodialis or warifteine inhibited allergen-induced AHR to inhaled methacholine and IL-13 levels in the bronchoalveolar lavage (BAL). In order to investigate the therapeutic potential of C. sympodialis and warifteine, animals were treated 1h after the last ovalbumin (OVA) challenge in sensitized animals. Similarly to the pre-treatment, post-treatment with warifteine was effective to inhibit significantly AHR to inhaled methacholine and to reduce IL-13 levels in the BAL. In addition, oral pre- or post-treatments with C. sympodialis or warifteine reduced OVA-induced eosinophil tissue infiltration, mucus production and subepithelial fibrosis to values similar to nonallergic controls. CONCLUSIONS: 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.