Ligustrazine, allicin and shear-induced platelet aggregation.

نویسندگان

  • F Liao
  • L Jiao
چکیده

Blood flow interacts with blood constituents and blood vessel under shear stress. Shear-induced platelet aggregation (SIPA) under high shear stress of stenosis has attracted research attention due to its involvement in vascular diseases, especially in life-threatening thrombosis. In SIPA, the calcium channel of platelet membrane can be activated by the interaction between plasma vWF and membrane GP Ib. As a consequence, SIPA occurs. SIPA has important implications because conventional anti-platelet drugs such as aspirin are of little use. The development of inhibitors of SIPA has been a pharmaceutical aim since the beginning of the 1990’s [1]. Here we show two potential alternatives. Ligustrazini hydrochloridi is an effective ingredient from Rhizoma ligustici Chuangxiong [2]. As a Chinese pharmaceutical product (in injection and oral form), it has been widely employed in vascular therapy since 1980. We have reported its effectiveness to inhibit SIPA [3]. Garlic is a spice for common cuisine as well as a herbal medicine. Allicin is mainly responsible for its pungent odor as well as its pharmacological benefit of anti-atherosclerotic effect [4]. Recently, we selected stenosis stress level of 52 dyn/cm2 and shear duration of 120 s to demonstrate the efficacy of ligustrazini and allicin on SIPA of New Zealand rabbits. The results show that the 50% inhibition concentration (IC50) of ligustrazine on SIPA was 0.52 mM. The IC50 of allicin was 1.27 mM. We further studied the mechanism by using monoclonal antibody of GP Ib and Fluo-3/AM with laser confocal microscope. We found that both compounds inhibited calcium channel in the platelet membrane without involvement in activating GP Ib. Ligustrazini of 0.22–0.88 mmol/l and allicin of 0.42–1.68 mmol/l significantly inhibited SIPA (P < 0.001) and calcium inflow (P < 0.01). Moreover, we conducted a pilot trial of 10 cardiovascular patients to determine ligustrazini’s effect on human SIPA, SIPA induced by stenosis level of stress was markedly inhibited by single dripping of ligustrazini of 80 mg, indicated by a decrease in SIPA of 12.0 ± 6.95% (P < 0.001). Susceptibility to atherosclerosis and stenosis of arteries in the elderly leads to the abnormally high wall shear stress of blood flow. SIPA is likely to happen in the cerebrovascular domain due to its high flow volume and velocity. Our research is at the junction of bio-mechanism, geriatrics, antithrombosis,

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عنوان ژورنال:
  • Clinical hemorheology and microcirculation

دوره 22 2  شماره 

صفحات  -

تاریخ انتشار 2000