title: Antiinflammatory and antiallodynic actions of the lignan niranthin isolated from Phyllanthus amarus. Evidence for interaction with platelet activating factor receptor.
abstract: 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.
authors.affiliation: Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, UFSC, Florianópolis, SC, Brazil.
authors.forename: Cândida A L
authors.initials: CA
authors.lastname: Kassuya
authors.forename: Aline
authors.initials: A
authors.lastname: Silvestre
authors.forename: Octávio
authors.initials: O
authors.lastname: Menezes-de-Lima
authors.forename: Denise Mollica
authors.initials: DM
authors.lastname: Marotta
authors.forename: Vera Lúcia G
authors.initials: VL
authors.lastname: Rehder
authors.forename: João B
authors.initials: JB
authors.lastname: Calixto
mesh_terms: D000700:Analgesics / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000840:Anisoles / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001381:Azepines / Q000494:pharmacology; D001667:Binding, Competitive; D002351:Carrageenan; D002540:Cerebral Cortex / Q000378:metabolism; D004149:Dioxoles / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D017705:Lignans / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D009195:Peroxidase / Q000037:antagonists & inhibitors; D029803:Phyllanthus; D010936:Plant Extracts / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects* / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013997:Time Factors; D014230:Triazoles / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000840:Anisoles; D000893:Anti-Inflammatory Agents; D001381:Azepines; D004149:Dioxoles; D017705:Lignans; D010936:Plant Extracts; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D013764:Tetrahydronaphthalenes; D014230:Triazoles; C039351:platelet activating factor receptor; C475932:niranthin; C475933:nirtetralin; D002351:Carrageenan; C063964:bepafant; D009195:Peroxidase