Previous studies have shown that the extracts obtained from Phyllanthus amarus, and some of the
lignans isolated from it, exhibit pronounced antiinflammatory properties. In the present study, we have assessed whether the antiinflammatory actions of these
lignans can be mediated by interaction with
platelet activating factor (PAF) receptor or interference with the action of this
lipid. The local administration of
nirtetralin, phyltetralin or
niranthin (30 nmol/paw), similar to
WEB2170 (a PAF receptor antagonist, 30 nmol/paw), significantly inhibited PAF-induced paw oedema formation in mice. The extracts of P. amarus (100 microg/ml) and
niranthin (30 microM), but not
nirtetralin or phyltetralin (30 microM), decreased the specific binding of [(3)H]-PAF in mouse cerebral cortex membranes. Furthermore, both
niranthin and
WEB2170 displaced, in a concentration-dependent manner, the [(3)H]-PAF binding sites. The mean IC(50) values from these effects were 6.5 microM and 0.3 microM, respectively. Additionally, both
niranthin and
WEB2170 (30 nmol/paw) inhibited the increase of
myeloperoxidase activity induced by PAF injection in the mouse paw. When assessed the mouse model of
pleurisy induced by PAF, pretreatment with
niranthin (100 micromol/kg, p.o.) or
WEB2170 (1.7 micromol/kg, i.p.) significantly inhibited PAF-induced
protein extravasations. Moreover, in the rat model of PAF-induced
allodynia, both
niranthin (30 nmol/paw) and
WEB2170 (30 nmol/paw) treatment significantly inhibited PAF-induced
allodynia. In addition,
niranthin had a rapid onset and long-lasting antiallodynic action when compared with
WEB2170. Collectively, the present findings suggest that
niranthin exhibits antiinflammatory and antiallodynic actions which are probably mediated through its direct antagonistic action on the PAF receptor binding sites.