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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1985 Feb;82(3):672–676. doi: 10.1073/pnas.82.3.672

Characterization of a platelet-activating factor receptor antagonist isolated from haifenteng (Piper futokadsura): specific inhibition of in vitro and in vivo platelet-activating factor-induced effects.

T Y Shen, S B Hwang, M N Chang, T W Doebber, M H Lam, M S Wu, X Wang, G Q Han, R Z Li
PMCID: PMC397107  PMID: 2983307

Abstract

Platelet-activating factor (PAF) is a potent lipid mediator of inflammation and asthma. Using a receptor preparation of rabbit platelet membranes, we identified a novel antagonist of PAF in the methylene chloride extract of a Chinese herbal plant, haifenteng (Piper futokadsura). The active antagonist, kadsurenone, was isolated and characterized in several in vitro and in vivo assays. It is a specific and competitive inhibitor of PAF binding to its receptor with a Ki of 5.8 X 10(-8) M vs. a Ki of 6.3 X 10(-9) M for PAF itself. It inhibits PAF-induced aggregation of rabbit platelets and human neutrophils at 2.4-24 microM, without showing any PAF agonistic activity. It potently inhibits PAF-induced degranulation of human neutrophils at 2.5-50 microM, also without any agonist activity. Kadsurenone is active orally at 25-50 mg/kg of body weight in blocking PAF-induced cutaneous permeability in the guinea pig. It also inhibits PAF-induced increases of hematocrit and circulating N-acetylglucosaminidase in the rat at greater than 10 mg/kg i.p. in a dose-dependent manner. Kadsurenone does not interfere with the function of several pharmacological mediators and receptors tested. Its structural specificity is evidenced by the poor PAF-antagonistic activities of three related structures isolated from the same haifenteng extract.

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Selected References

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