Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, 350116, China.
Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350116, China.
Sci Rep. 2017 Jul 19;7(1):5813. doi: 10.1038/s41598-017-05825-9.
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.
最近，全球放宽了对人参作为餐桌食品的监管，这引起了我们的担忧，即服用华法林预防致命性中风和血栓栓塞的患者在使用人参产品恢复生物能量时，可能会与人参发生危及生命的相互作用。在这里，我们表明，从人参中提取的质量控制人参皂苷，含有其主要活性成分，在大鼠体内产生剂量和时间依赖性拮抗作用，对抗华法林的抗凝作用，这是通过 INR 和大鼠血栓模型来评估的。通过血栓分析仪、UPLC/MS/MS、ELISA 和实时 PCR，分别确定了人参皂苷与华法林在血栓形成、药代动力学、凝血因子和肝细胞色素 P450 异构体活性方面的相互作用。这种拮抗作用与相关的药代动力学相互作用很好地相关，表明在与华法林共同给药三周后，一周华法林给药后达到的华法林血药浓度显著降低，而 7-羟基华法林增加。一周华法林和三周华法林-人参皂苷方案导致凝血因子 II、VII 和蛋白 Z 的水平被华法林抑制得到恢复，并显著增强了代谢华法林的 P450 3A4 和 2C9 的活性。本研究首次提供了确凿的证据，证明了华法林-人参皂苷相互作用，并警告华法林使用者和监管机构注意这种危险的相互作用。
