Umar Anwar, Guerin Viviane, Renard Martine, Boisseau Michel, Garreau Charles, Begaud Bernard, Molimard Mathieu, Moore Nicholas
Département de Pharmacologie, EA525, Université Victor Segalen, 33076 Bordeaux, France.
Thromb Res. 2003 May 1;110(2-3):135-40. doi: 10.1016/s0049-3848(03)00343-8.
The "French paradox", a low cardiovascular mortality compared to the prevalent risk factors, has been attributed to the regular use of red wine, and to the polyphenols it contains. These have among other effects an antioxidant and antithrombotic effect. The French paradox is maximal in southwest France, a region which is the region of production of armagnac, an oak cask aged spirit also rich in polyphenols.
We tested the effects of a freeze-dried extract of 12-year-old armagnac (EA88) on in vitro human platelet adhesion, and on aggregation induced by collagen or ADP, in the presence or absence of hypoxanthine-xanthine oxidase (HX/XO), at concentrations ranging from 5 x 10(-9) to 5 x 10(-3) g/l, after 15-60 min incubation. We also tested the effects of 2-week oral treatment with 1, 5 and 25 mg/kg EA88 in a rat arteriovenous shunt thrombosis model.
EA88 inhibited ADP-induced but not collagen-induced human platelet aggregation in vitro in a concentration- and incubation time-dependent manner, which was greater in the presence of HX/XO. In vivo, giving rats a daily oral dose of EA88 for 2 weeks inhibited thrombus formation in a dose-dependent manner, for doses consistent with the habitual human use of armagnac.
Armagnac extract EA88 had an antiplatelet and antithrombotic effect that if confirmed in man could contribute to explain the intensity of the French paradox in southwest France.
“法国悖论”指的是,尽管存在常见的心血管疾病风险因素,但法国的心血管疾病死亡率却较低,这一现象被归因于人们经常饮用红酒及其所含的多酚类物质。这些多酚类物质具有多种功效,其中包括抗氧化和抗血栓作用。法国西南部地区的“法国悖论”最为明显,该地区是阿马尼亚克酒的产地,这种经橡木桶陈酿的烈酒也富含多酚类物质。
我们测试了12年陈酿阿马尼亚克酒的冻干提取物(EA88)对体外人血小板黏附以及在有无次黄嘌呤 - 黄嘌呤氧化酶(HX/XO)存在的情况下,由胶原蛋白或二磷酸腺苷(ADP)诱导的血小板聚集的影响,浓度范围为5×10⁻⁹至5×10⁻³ g/l,孵育15 - 60分钟后进行测试。我们还在大鼠动静脉分流血栓形成模型中测试了以1、5和25 mg/kg的剂量对EA88进行为期2周的口服治疗的效果。
EA88在体外以浓度和孵育时间依赖性方式抑制ADP诱导的而非胶原蛋白诱导的人血小板聚集,在HX/XO存在的情况下这种抑制作用更强。在体内,给大鼠每日口服EA88 2周,对于与人类习惯饮用阿马尼亚克酒剂量相当的给药量,能以剂量依赖性方式抑制血栓形成。
阿马尼亚克酒提取物EA88具有抗血小板和抗血栓作用,如果在人体中得到证实,可能有助于解释法国西南部地区“法国悖论”的显著程度。