Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans
Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans
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DOI：
10.1111/j.1538-7836.2004.01067.x
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发表时间：
2004-12-01
影响因子：
10.4
通讯作者：
Gibbins, JM
中科院分区：
文献类型：
--
作者：
Hubbard, GP;Wolffram, S;Gibbins, JM
背景：槲皮素是人类饮食中存在的一种类黄酮，在洋葱、苹果、茶和葡萄酒中含量很高，此前已被证明可以在体外抑制血小板聚集和信号传导。因此，有人提出，槲皮素可能有助于富含水果和蔬菜的饮食对心血管疾病的保护作用。目的：一项人类饮食干预试验研究旨在研究膳食槲皮素的摄入与血小板功能之间的关系。方法：人类受试者摄入 150 毫克或 300 毫克槲皮素-4'-O-β-D-葡萄糖苷补充剂，以确定槲皮素的全身利用率。从受试者身上分离血小板以分析胶原蛋白刺激的细胞信号传导和聚集。结果：摄入 150 mg 和 300 mg 剂量的槲皮素-4'-O-β-D-葡萄糖苷后 30 分钟，血浆槲皮素浓度分别达到 4.66 mum (+/-0.77) 和 9.72 mum (+/-1.38) 峰值，表明槲皮素具有生物利用度，血浆浓度达到已知影响血小板功能的范围。体外。摄入两个剂量的槲皮素-4'-O-β-D-葡萄糖苷后30和120分钟，血小板聚集受到抑制。相应地，胶原刺激的总血小板蛋白酪氨酸磷酸化被抑制。这是由于酪氨酸激酶 Syk 和磷脂酶 Cgamma2（血小板糖蛋白 VI 胶原蛋白受体信号通路的组成部分）的酪氨酸磷酸化减少所致。结论：这项研究提供了新的证据，证明通过补充槲皮素-4'-O-β-D-葡萄糖苷形式的槲皮素具有相对较高的全身利用率，并表明槲皮素是血小板细胞信号传导和血栓形成的饮食抑制剂。
Background: Quercetin, a flavonoid present in the human diet, which is found in high levels in onions, apples, tea and wine, has been shown previously to inhibit platelet aggregation and signaling in vitro. Consequently, it has been proposed that quercetin may contribute to the protective effects against cardiovascular disease of a diet rich in fruit and vegetables. Objectives: A pilot human dietary intervention study was designed to investigate the relationship between the ingestion of dietary quercetin and platelet function. Methods: Human subjects ingested either 150 mg or 300 mg quercetin-4'-O-beta-D-glucoside Supplement to determine the systemic availability of quercetin. Platelets were isolated from subjects to analyse collagen-stimulated cell signaling and aggregation. Results: Plasma quercetin concentrations peaked at 4.66 mum (+/-0.77) and 9.72mum (+/-1.38) 30min after ingestion of 150-mg and 300-mg doses of quercefin-4'-O-beta-D-glucoside, respectively, demonstrating that quercetin was bioavailable, with plasma concentrations attained in the range known to affect platelet function in vitro. Platelet aggregation was inhibited 30 and 120 min after ingestion of both doses of quercetin-4'-O-beta-D-glucoside. Correspondingly, collagen-stimulated tyrosine phosphorylation of total platelet proteins was inhibited. This was accorripanied by reduced tyrosine phosphorylation of the tyrosine kinase Syk and phospholipase Cgamma2, components of the platelet glycoprotein VI collagen receptor signaling pathway. Conclusions: This study provides new evidence of the relatively high systemic availability of quercetin in the form of quercetin-4'-O-beta-D-glucoside by supplementation, and implicates quercetin as a dietary inhibitor of platelet cell signaling and thrombus formation.