Biological and Pharmacological Effects of Pinusolide, a Novel Platelet Activating Factor Antagonist

Abstract

Pinusolide, a potent platelet activating factor (PAF) receptor binding antagonist, inhibited PAF-induced aggregation of rabbit platelets with an IC₅₀ value of 5 µM, whereas no inhibitory effects on the aggregation induced by ADP, thrombin, and collagen were observed. Pinusolide protected the mice from PAF-induced lethality with ED₅₀ values of 1.1 mg/kg, i.v. and 69 mg/kg, p.o. Topically given pinusolide at 2 mg/ear effectively inhibited croton oil induced mouse ear edema. All the pinusolide treated ears recovered to normal healthy appearance in a sharp contrast to totally necrotized untreated ears. These results indicated that pinusolide is a potent and specific PAF antagonist in all experimental models as shown in vitro, in vivo, and in animal tests.

Key words

Platelet activating factor (PAF) antagonist - Biota orientalis - Cupressaceae - pinusolide - PAF-induced lethality - croton oil - topical anti-inflammatory activity