Global deregulation of ginseng products may be a safety hazard to warfarin takers: solid evidence of ginseng-warfarin interaction
Global deregulation of ginseng products may be a safety hazard to warfarin takers: solid evidence of ginseng-warfarin interaction
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全球人参产品放松管制可能对华法林服用者构成安全隐患：人参与华法林相互作用的确凿证据
DOI：
10.1038/s41598-017-05825-9
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发表时间：
2017-07-19
影响因子：
4.6
通讯作者：
Jia, Lee
中科院分区：
文献类型：
--
作者：
Dong, Haiyan;Ma, Ji;Jia, Lee
最近全球放松对人参作为餐桌食品的管制，引起了我们对人参-华法林相互作用的担忧，这种相互作用可能危及服用华法林预防致命性中风和血栓栓塞的患者的生命，同时使用人参产品进行生物能量恢复。在这里，我们表明，从人参中提取并含有其主要活性成分的质量控制人参皂苷，在大鼠中产生剂量和时间依赖性拮抗华法林的抗凝作用，通过INR和大鼠血栓形成模型进行评估。采用血栓分析仪、UPLC/MS/MS、ELISA和实时荧光PCR等方法，研究了黄芩苷和华法林对血栓形成、药代动力学、凝血因子活性和肝细胞色素P450异构体的影响。这种拮抗作用与相关的药代动力学相互作用密切相关，表明华法林给药一周后达到的华法林血平台在华法林与甘草苷联合给药三周后显著降低，而7-羟基华法林增加。一周华法林和三周华法林-β-糖苷方案导致恢复华法林抑制的β-凝血因子II、VII和蛋白Z的水平，并显著增强代谢华法林的P450 3A 4和2C 9的活性。本研究首次提供了华法林与华法林相互作用的确凿证据，并警告华法林使用者和监管当局注意这种危险的相互作用。
Recent global deregulation of ginseng as the table food raises our concern about the possible ginseng-warfarin interaction that could be life-threatening to patients who take warfarin for preventing fatal strokes and thromboembolism while using ginseng products for bioenergy recovery. Here we show that quality-control ginsenosides, extracted from ginseng and containing its major active ingredients, produce dose-and time-dependent antagonism in rats against warfarin's anti-coagulation assessed by INR and rat thrombosis model. The interactions between ginsenosides and warfarin on thrombosis, pharmacokinetics, activities of coagulation factors and liver cytochrome P450 isomers are determined by using thrombosis analyzer, UPLC/MS/MS, ELISA and real-time PCR, respectively. The antagonism correlates well with the related pharmacokinetic interaction showing that the blood plateaus of warfarin reached by one-week warfarin administration are significantly reduced after three-week co-administration of warfarin with ginsenosides while 7-hydroxywarfarin is increased. The one-week warfarin and three-week warfarin-ginsenosides regimen result in restoring the suppressed levels by warfarin of the coagulating factors II, VII and protein Z, and significantly enhance activities of P450 3A4 and 2C9 that metabolize warfarin. The present study, for the first time, provides the solid evidence to demonstrate the warfarin-ginsenoside interaction, and warns the warfarin users and regulation authorities of the dangerous interaction.