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Abstract：
Ginseng is often prescribed together with cisplatin for treatment of cancer, but the interaction between ginseng and cisplatin is still unknown. This study employed ginsenoside Rb1 (Rb1), one of the major components in ginseng, to explore the effects and involved mechanisms of cisplatin on the pharmacokinetics of ginseng. The effects of cisplatin on the pharmacokinetics of Rb1 and its bioactive metabolites Rd, Rg3, and F2 were investigated by using A549-bearing mice with and without cisplatin intervention. Our data showed that cisplatin could significantly decrease the AUC(0-t) and Cmax of Rd, Rg3, and F2, except Rb1. To evaluate the involved mechanisms, feces and intestinal mucosa were collected to explore the effects of cisplatin on the gut metabolism of Rb1 in vitro; meanwhile, Caco-2 cell model and small intestine histological characters were examined to evaluate the effects of cisplatin on the gut absorptive areas and permeability. The mechanisms involved may be mainly related to the comprehensive contributions of inhibited intestinal bacteria and mucosa metabolisms, narrowed intestinal absorptive area, increased efflux ratio of intestinal absorption and enhanced intestinal permeability. All these findings suggested that the dosage of ginseng traditionally used for health protection should be adjusted when it was prescribed together with cisplatin in the treatment of cancer.
摘要：
人参通常与顺铂一起用于治疗癌症，但是人参和顺铂之间的相互作用仍然未知。本研究采用人参皂苷Rb1（Rb1），人参的主要成分之一，探讨顺铂对人参药动学的影响及相关机制。顺铂对Rb1及其生物活性代谢产物Rd,Rb1药代动力学的影响,通过使用带有和不带有顺铂干预的A549小鼠研究Rg3和F2。我们的数据显示，顺铂可以显着降低Rd的AUC（0-t）和Cmax，Rg3和F2，Rb1除外。为了评估所涉及的机制，收集粪便和肠黏膜,探讨顺铂对体外肠道Rb1代谢的影响;同时,检查Caco-2细胞模型和小肠组织学特征，以评估顺铂对肠道吸收面积和通透性的影响。其机制可能主要与抑制肠道细菌和黏膜代谢的综合作用有关。缩小肠道吸收面积，肠吸收外排率增加，肠通透性增强。所有这些发现都表明，在与顺铂一起治疗癌症时，应调整传统上用于健康保护的人参剂量。
