三七蒸制前后主要活性成分体内药动学及其抗血小板聚集活性比较研究

目的研究不同蒸制时间(0、2、4、8 h)三七主要活性成分变化、体内药动学和抗血小板聚集活性之间的关系。方法采用高效液相色谱(HPLC-UV)法分析三七蒸制前后主要活性成分变化;大鼠ig 500 mg/kg不同蒸制时间的三七样品液后于不同时间点眼眶取血,超高效液相色谱-串联质谱(UPLC-MS/MS)法测定三七蒸制前后主要皂苷的血药浓度,运用DAS 3.2.6软件计算各成分的药动学参数;采用PAPE-I型血小板聚集/血凝测定仪检测抗血小板聚集活性。结果蒸制过程降低了生物活性物质三七皂苷R_1及人参皂苷Rg_1、Rd、Rb_1、Re的水平,并产生了新的成分人参皂苷Rg_2、Rg_3、Rh_1、F_2、Rk_3、Rh_4。人参皂苷Rb_1、Rd的脱糖基代谢产物人参皂苷Rg_3与原型皂苷人参皂苷Rb_1比较,t_(max)略有降低,表明脱糖基之后吸收速度加快。蒸三七比生三七有更明显的抗血小板聚集活性,且随着蒸制过程的延长,抗血小板聚集活性更强。结论三七蒸制后,皂苷类成分脱糖基后可能产生活性更强的成分,某些脱糖基代谢产物更易吸收入血,可能导致抗凝血活性增强。

Comparative study on contents and pharmacokinetics of raw and steamed Notoginseng Radix et Rhizoma and its anti-platelet aggregation activity

Objective To compare the relationship of ingredients and pharmacokinetics of steamed Notoginseng Radix et Rhizoma(the roots of Panax notoginseng) with different time(0, 2, 4, and 8 h), and accompany with its anti-platelet aggregation activity. Methods The components with different steaming duration were determined by HPLC method. Concentration of saponins in Notoginseng Radix et Rhizoma before and after steaming at different time points were detected by UPLC-MS/MS. Pharmacokinetic parameters of each compound were calculated using DAS 3.2.6 software. The anti-platelet aggregation activity was measured by platelet aggregation/clotting analyzer. Results The results showed that the steaming process reduced the contents of certain bioactive substances(NG-R₁, Rg₁, Rd, Rb₁, and Re) and produced some new components(Rh₁, Rg₃, Rk₃, and Rh₄). Ginsenoside Rg₃, deglycosylated metabolites of ginsenoside Rb₁ possessed lower t_max than ginsenoside Rb₁ that indicated the course of deglycosylation made faster absorption. Steamed Notoginseng Radix et Rhizoma had stronger antiplatelet activity, following higher antiplatelet and anticoagulant activities with increasing steaming durations. Conclusion The results inspire us that saponins may become more active ingredients after deglycosylation, saponins with deglycosylated in vitro become more and more active ingredients into the blood, which could make stronger anticoagulant activity.