Inhibition of allergen-induced eosinophil recruitment by natural tetranortriterpenoids is mediated by the suppression of IL-5, CCL11/eotaxin and NFkappaB activation.

The present study reports the anti-allergic activity of a group of six different tetranortriterpenoids (TNTP) isolated from the seeds of Carapa guianensis Aublet: 6a-acetoxygedunin, 7-deacetoxy-7-oxogedunin, andirobin, methyl angolensate, 6a-acetoxyepoxyazadiradione and gedunin. Oral pretreatment with TNTP significantly inhibited total leukocyte and eosinophil accumulation in C57BL/10 mice pleural cavities 24 h after the intrathoracic (i.t.) injection of ovalbumin (OVA), but had no effect on CD4, CD8 or gammadelta T lymphocyte accumulation. Pleural washes recovered from 6 h OVA-stimulated mice (OPW) pretreated with TNTP failed to induce shape change in eosinophil in vitro, indicating the inhibition of eosinophilotactic chemokines by TNTP. In accordance with such results, ELISA assays showed decreased levels of CCL11/eotaxin and IL-5 in OPW recovered from TNTP pretreated mice within 6 h. TNTP oral pretreatment inhibited nuclear factor-kappaB (NFkappaB) translocation into the nucleus in pleural leukocytes recovered from previously sensitized mice after antigenic challenge. In addition, the incubation of splenocytes recovered from previously sensitized mice with TNTP also inhibited NFkappaB activation after OVA stimulation. Taken together, these results indicate that the inhibition of allergic eosinophilia by TNTP is correlated with the inhibition of CCL11/eotaxin and IL-5 generation through NFkappaB signaling pathway impairment in mice.