Antiinflammatory and antiallodynic actions of the lignan niranthin isolated from Phyllanthus amarus -: Evidence for interaction with platelet activating factor receptor

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 PAY receptor antagonist, 30 nmol/paw), significantly inhibited PAF-induced paw oedema formation in mice. The extracts of P. amarus (100 mu g/ml) and niranthin (30 mu M), but not nirtetralin or phyltetralin (30 mu M), decreased the specific binding of [H-3]-PAF in mouse cerebral cortex membranes. Furthermore, both niranthin and WEB2170 displaced, in a concentration-dependent manner, the [H-3]-PAF binding sites. The mean IC50 values from these effects were 6.5 mu M and 0.3 mu M, 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 PAT, pretreatment with niranthin (100 mu mol/kg, p.o.) or WEB2170 (1.7 mu mol/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-induccd 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 anti inflammatory and antiallodynic actions which are probably mediated through its direct antagonistic action on the PAF receptor binding sites. (c) 2006 Elsevier B.V. All rights reserved.