Inhaled Cissampelos sympodialis Down‐Regulates Airway Allergic Reaction by Reducing Lung CD3⁺T Cells

Abstract

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‐asthmatic and anxiolytic effects of Herissantia tiubae, a Brazilian medicinal plant

“…There are at least two different ways whereby allergic challenge could affect respiratory measures. Firstly, similar to previous reports , we found extensive mucus secretion in the airways of challenged animals. The resulting increase in the respiratory resistance would prevent the fast‐frequency breathing/sniffing due to inability to rapidly inflate/deflate the lungs.…”

“…In examining the population of CD3 + T‐lymphocytes, we observed a significant reduction of these cells in animals treated with HtE. Similar results were demonstrated with Cissampelos sympodialis extract, where the reduction of CD3 + cells in the BAL was correlated with a beneficial immunomodulation of asthma . In addition, HtE treatment, especially at dose of 50 mg/kg, decreased percentage of B220+ cells (B cells) in BAL.…”

Ethanol extract of Cissampelos sympodialis ameliorates lung tissue damage in streptozotocin-induced diabetic rats

“…(Barbosa Filho, Agra, Thomas, 1997;Marinho, Barbosa-Filho, Oliveira, 2012;Aragão, 2012) Crude ethanolic extract was standardized using warifteine and methylwarifteine as markers that were also found in the total alkaloid fraction (TAF-Cs) [16,17]. Studies were carried out with these components and showed different pharmacological effect on the hepatic (Melo et al, 2003), nervous (Almeida et al, 2005), cardiovascular (Cavalcante et al, 2011), immune (Vieira et al, 2012) and gastrointestinal systems (De Sales et al, 2015). Several studies demonstrated that the respiratory system exhibited improved function in an experimental model of allergic asthma (Batista- Lima et al, 2001;Costa et al, 2008;Cerqueira-Lima et al, 2010;Bezerra-Santos et al, 2012, Vieira et al, 2013.…”

Warifteine Therapeutic Treatment Reduced Leukocyte Recruitment and Anxiety-Like Response in Ovalbumin-Induced Allergic Pulmonary Inflammation / Tratamento Terapêutico Com Warifteína Reduz Recrutamento De Leucócitos E Resposta Semelhante Á Ansiedade Na Inflamação Pulmonar Alérgica Induzida Por Ovalbumina

“…In this study, therapeutic treatment with warifteine also inhibited neutrophil migration but not lymphocytes and macrophages into the BALF. This phenomena might be explained considering the warifteine administration route and its different effect on the leukocyte recruitment as observed in a previous study which revealed macrophages and lymphocytes reduced numbers into the BALF in OVA-sensitized mice treated by nasal instillation with warifteine [46].…”

“…Cissampelos sympodialis Eichler (Menispermaceae) is an endemic species of Northeastern Brazil, whose leaves and roots are used in indigenous and popular medicine in the treatment of several inflammatory diseases, including asthma [19,20]. The bisbenzylisoquinoline alkaloid warifteine, isolated from C. sympodialis represents the major compound of the plant and its properties have been reported such as anti-inflammatory, anti-allergic, immunomodulatory and psychoactive in several experimental models [21][22][23][24][25][26][27][28][29][30][31]. Thus, the main objective of this study was to evaluate the oral therapeutic treatment with the alkaloid warifteine in anxiety-like response, respiratory rate and leukocyte recruitment in an experimental model of allergic pulmonary inflammation.…”