The isolation and characterization of kadsurenone from haifenteng (Piper futokadsura) as an orally active specific receptor antagonist of platelet-activating factor.
A natural product, kadsurenone, was isolated from the Chinese herbal preparation haifenteng (Caulis piperis futokadsurae) and characterized as an orally-active specific antagonist of the platelet-activating factor (PAF). Kadsurenone inhibits the specific binding of 3H-PAF to a receptor preparation from rabbit platelet membrane in a competitive and reversible manner, its Ki being 3.88 X 10(-8) M. It inhibits the aggregation of rabbit platelets in plasma induced by PAF with a pA2 of 6.28, but not those induced by arachidonic acid, epinephrine, ADP or A-23187. It inhibits the aggregation of isolated human neutrophils with a pA2 of 6.32. It also inhibits PAF-induced degranulation and release of beta-D-glucuronidase at 2-24 microM in vitro. In the rat, kadsurenone at 8-40 mg/kg i.p. inhibits the increases of plasma lysosomal enzymes and haematocrit induced by intravenous PAF. In the guinea pig, kadsurenone at 25-50 mg/kg p.o. reduces the increase of cutaneous vascular permeability induced by PAF. These results indicate that kadsurenone is a specific and effective receptor antagonist of PAF in several in vitro and in vivo systems.
D000818:Animals; D001572:Benzofurans; D001578:Benzopyrans / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D001667:Binding, Competitive; D002199:Capillary Permeability / Q000187:drug effects; D006168:Guinea Pigs; D006801:Humans; D017705:Lignans; D008247:Lysosomes / Q000201:enzymology; D009504:Neutrophils / Q000187:drug effects; D010946:Plants, Medicinal / Q000032:analysis*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins; D011817:Rabbits; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled
D001572:Benzofurans; D001578:Benzopyrans; D017705:Lignans; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C044540:kadsurenone