黄芪、赤芍配伍补骨脂对大鼠体内补骨脂素和异补骨脂素药代动力学的影响

Interactions of Psoralea corylifolia L.with Astragali Radix and Paeoniae Radix Rubra in rats based on pharmacokinetics

目的 研究黄芪、赤芍与补骨脂配伍后,补骨脂中主要毒性成分补骨脂素和异补骨脂素的血浆药代动力学参数变化。方法 32只雄性SD大鼠随机分为4组,补骨脂组、补骨脂-黄芪组、补骨脂-赤芍组、补骨脂-黄芪-赤芍组。单次灌胃给药,分别于给药后0.25、0.5、0.75、1、2、4、6、8、10、12、24 h目内眦取血,超高效液相色谱-串联四级杆质谱(UPLC-MS/MS)法检测血浆中补骨脂素和异补骨脂素的血药浓度,采用DAS3.0软件非房室模型计算药动学参数。结果 补骨脂与赤芍配伍后,大鼠血浆中补骨脂素、异补骨脂素最高血药浓度(c_(max))、药时曲线下面积(AUC_(0-t))显著降低,补骨脂与黄芪配伍后,大鼠血浆中异补骨脂素的c_(max)显著降低,补骨脂与黄芪赤芍三药合用后大鼠血浆中补骨脂素和异补骨脂素的AUC_(0-t)显著降低;异补骨脂素的AUC_(0-∞)和c_(max)显著降低。结论 黄芪、赤芍与补骨脂配伍使用,可以降低补骨脂中主要毒性成分补骨脂素和异补骨脂素的体内暴露量,补骨脂-黄芪-赤芍组大鼠血浆中异补骨脂素平均驻留时间(MRT)延长,其具体作用机制有待深入研究。

Objective To study the changes of plasma pharmacokinetic parameters of psoralen and isopsoralen,the main toxic components of psoralen,after the compatibility of Astragali Radix,Paeoniae Radix Rubra and Psoralea corylifolia L..Methods Thirty-two male SD rats were randomly divided into four groups:Psoralea corylifolia L.group,Psoralea corylifolia L.-Astragali Radix group,Psoralea corylifolia L.-Paeoniae Radix Rubra group,Psoralea corylifolia L.-Astragali Radix-Paeoniae Radix Rubra group.Blood was collected from the inner canthus at 0.25,0.5,0.75,1,2,4,6,8,10,12,and 24 h after single intragastric administration.Plasma concentrations of psoralen and isopsoralen were detected with the UPLC-MS/MS method,and pharmacokinetic parameters were calculated via a non-attoventricular model using DAS3.0 software.Results The c_(max) and AUC of psoralen and isopsoralen decreased significantly when Psoralea corylifolia L.was combined with Paeoniae Radix Rubra,so did the c_(max) of isopsoralen in rat plasma when Psoralea corylifolia L.was combined with Astragali Radix.However,after the combination of Psoralea corylifolia L.and Astragali Radix and Paeoniae Radix Rubra,the AUC_(0-t) of psoralen and isopsoralen decreased significantly in rat plasma,so did the AUC_(0-∞)and c_(max) of isopsoralen.Conclusion The combination of Astragali Radix,Paeoniae Radix Rubra and Psoralea Corylifolia L.can reduce the exposure of psoralen and isopsoralen in vivo.Paeoniae Radix Rubra or Astragali Radix plus Psoralea corylifolia L.can reduce plasma c_(max) and AUC_(0-t),but the MRT of isopsoralen in plasma of rats in the Psoralea corylifolia L.-Astragali Radix-Paeoniae Radix Rubra group is prolonged,the specific mechanism of which needs to be further studied.