Pinusolide from the leaves of Biota orientalis as potent platelet activating factor antagonist

• Published in: Planta medica Vol. 65; no. 1; pp. 39 - 42
• Main Authors: Kim, K.A, Moon, T.C, Lee, S.W, Chung, K.C, Han, B.H, Chang, H.W
• Format: Journal Article
• Language: English
• Published: Germany 01.02.1999
• Subjects: Animals; antagonists; blood platelets; Blood Pressure - drug effects; Capillary Permeability - drug effects; cardiovascular system; Cupressaceae; Diterpenes - isolation & purification; Diterpenes - pharmacology; diterpenoids; dosage; dose response; hypotension; inhibition; leaves; Male; medicinal properties; Plant Leaves - chemistry; Plants - chemistry; Platelet Activating Factor - antagonists & inhibitors; platelet-activating factor; Rabbits; Rats; Rats, Sprague-Dawley; serotonin
• ISSN: 0032-0943; 1439-0221
• DOI: 10.1055/s-1999-13959

We investigated the effect of a new PAF antagonist pinusolide, isolated from the leaves of Biota orientalis, on PAF-induced [3H]serotinin release from rabbit platelets, hypotension and vascular permeability. Pinusolide (IC50, about 5 x 10(-6) M) inhibited specifically [3H]serotinin release from rabbit platelets when stimulated with PAF (5 x 10(-8) M), but showed no effect when induced by ADP, collagen, and thrombin. It also inhibited PAF-induced hypotension in a dose-dependent manner in rats with no effect on the hypotension induced by acetylcholine, histamine and serotonin. The inhibitory effect of pinusolide on the PAF-induced vascular permeability is less specific than the induced hypotension. These results suggest that pinusolide may prove of therapeutic value in the treatment of hypotension and a molecular design of pinusolide analogues may provide the possibility of a new PAF specific antagonists.