Investigação do efeito anti-inflamatório dos alcaloides warifteina e metil-warifteina de cissampelos sympodialis EICHL. (menispermaceae) em modelos de inflamação aguda e crônica

Abstract

Root bark infusions of the plant Cissampelos sympodialis Eichl (Menispermaceae) are used in folk medicine, in Northeast Brazil, for the treatment of diseases of the respiratory and digestive tracts. Previous studies showed that the hydroalcoholic extract of the leaves (AFL) of the plant and warifteine (W), alkaloid bisbenzylisoquinolinic, presented anti-inflammatory and anti-allergic effects. This study evaluated the effect of the oral treatment of mice with W and methyl warifteine (MW) in the paw edema formation induced by phlogistic agents, vascular leakage and cell migration in acute inflammatory models and the effect of oral treatment with AFL and its alkaloids (W and MW) in chronic inflammation represented by the experimental model of food allergy (BALB / c mice sensitized with ovalbumin - OVA). Oral treatment with W reduced the paw edema induced by carrageenan, histamine and prostaglandin E2, an effect not presented in MW treatment. The warifteine and methyl-warifteine also reduced the vascular leakage, however without inhibiting cell migration associated with inflammation. In the experimental model of food allergy the treatment with W induced weight gain in animals with decreased of diarrhea. Methylation of warifteine did not induce weight gain nor inhibited allergic diarrhea during the allergen challenge. However treatment with AFL did not induce weight gain nor inhibited allergic diarrhea. In contrast, treatment with the AFL or its alkaloids reduced the IgE specific for ovalbumin (OVA) titer, increased the proportion of CD4 + or CD8+ T lymphocytes in mesenteric lymph nodes. The proportion of regulatory T lymphocytes in the mesenteric lymph nodes was also increased by the treatments. In vitro experiments, with cells from mesenteric lymph nodes of sensitized animals, demonstrated that W and MW inhibited the secretion of interleukin (IL-) 12 and IL-10 with no change in the interferon-γ (IFN-γ) and IL- 13 levels. These results demonstrated that the oral treatment with warifteine presented anti-inflammatory activity by inhibiting the action of mediators of inflammation and the methylation of the molecule did not improve this effect. Also, the treatment with AFL, W and MW showed immunomodulatory effects in food allergy with increased of Treg cells and decreased of cytokines derived from cells of the innate immune mechanism independent of that of the adaptive immune mechanism.