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