Antiplatelet and Vasorelaxing Actions of the Acetoxy Derivative of Cedranediol Isolated from Juniperus squamata

Abstract

The antiplatelet and vasorelaxing actions of 14-acetoxycedrol, an acetyl derivative of the sesquiterpene 8,14-cedranediol isolated from Juniperus squamata Hayata, were investigated in washed rabbit platelets and rat aorta, respectively. 14-Acetoxycedrol inhibited the aggregation and ATP release of rabbit platelets induced by ADP, arachidonic acid, platelet-activating factor (PAF), collagen, and thrombin. Prolongation of the incubation time of 14-acetoxycedrol with platelets did not cause further inhibition and the aggregability of the treated platelets could be restored after washing of the platelets. It inhibited thromboxane B₂ formation of washed platelets caused by arachidonic acid, collagen, and thrombin in a concentration-dependent manner. The formation of inositol phosphate caused by collagen and PAF was inhibited by 14-acetoxycedrol, while that caused by thrombin was not affected. 14-Acetoxycedrol markedly inhibited the intracellular calcium rise caused by PAF, and slightly inhibited that caused by thrombin in quin-2/AM-load platelets. In rat thoracic aortae, 14-acetoxycedrol inhibited the high K⁺ (60 mM) and Ca²⁺ (0.03 - 3 mM) induced cumulative contractions in a concentration-dependent manner, while it did not affect the phasic and tonic contractions elicited by norepinephrine. The tonic contractions elicited by KCl (60 mM) and Bay K 8644 were also relaxed by 14-acetoxycedrol. It is concluded that the antiplatelet effect of 14-acetoxycedrol is due to the inhibition of thromboxane formation and phosphoinositides breakdown and the vasorelaxing action of 14-acetoxycedrol is due to inhibition of Ca²⁺ influx through the voltage-dependent Ca²⁺ channel.

Key words

14-Acetoxycedrol - Juniperus squamata - Cupressaceae - antiplatelet - vasorelaxation - Ca²⁺-channel blocker - thromboxane formation