In this study we examined the ability of the furofuran
lignan yangambin to influence the local and systemic responses induced by
antigen or PAF in actively sensitized or normal rats. Given intraperitoneally 1 h before stimulation,
yangambin inhibited the pleural neutrophil and eosinophil infiltration evoked by the i.pl. injection of PAF or
antigen into normal or 14 daysensitized rats whereas plasma exudation evoked by both stimuli was unaffected. The pleural neutrophil influx (6 h) after
LTB4 stimulation was also significantly inhibited by
yangambin. We also evidenced that the hemoconcentration,
thrombocytopenia, and leucocytosis noted after i.v. PAF were all attenuated by
yangambin. In actively sensitized rats, pretreatment with
yangambin failed to modify the
antigen-induced hemoconcentration and leucocytosis, but dose-dependently abrogated the
thrombocytopenia noted 1 h post-stimulation. In vitro, the anaphylactic contraction of longitudinal jejunal segments to
antigen challenge was significantly inhibited by
yangambin (10(-5)-10(-4) M). Likewise, the contraction of jejunal segments from normal rats to PAF was markedly blocked by
yangambin under conditions where the response to
5-hydroxytryptamine (5-HT) was not altered. In conclusion, our results show that
antigen- and PAF-induced pleural neutrophil and eosinophil accumulation, but not exudation, is sensitive to treatment with
yangambin. In addition,
yangambin also suppressed the pleural neutrophil infiltration triggered by
LTB4 as well as the blood
thrombocytopenia and intestinal
anaphylaxis elicited by
antigen in rats. Thus, our findings indicate that
yangambin shows an antagonistic action on receptors other than those of PAF, i.e.,
LTB4, and strongly suggest that it may be a useful
drug in the treatment of some allergic inflammatory responses.