补骨脂13种活性成分在正常与酒精性肝病大鼠中的药动学比较

    Comparative Pharmacokinetics of 13 Bioactive Components of Psoraleae Fructus in Normal and Alcoholic Liver Disease Rats

    • 摘要:
      目的 采用超高效液相色谱-串联质谱(UHPLC-MS/MS)技术探究补骨脂中补骨脂素、异补骨脂素、补骨脂酚、补骨脂查尔酮、补骨脂二氢黄酮甲醚、补骨脂宁、补骨脂定、补骨脂甲素、补骨脂乙素、异补骨脂二氢黄酮、新补骨脂异黄酮、巴库查尔酮和corylifol A 13种成分在正常大鼠和酒精性肝病(alcoholic liver disease,ALD)模型大鼠的体内药动学。
      方法 使用Hypersil GOLD C18色谱柱(2.1 mm×100 mm,1.9 μm),流动相为水-乙腈,梯度洗脱,流速0.2 mL·min−1,柱温为40 ℃。在成功建立SD大鼠的ALD模型基础上,按1.07 g·kg−1的剂量灌胃给药补骨脂生药溶液,采用UHPLC-MS/MS测定血浆中13种主要入血成分的血药浓度,药动学软件 DAS 3.0 计算各成分的药动学参数。
      结果 SD大鼠在患ALD后服用补骨脂,补骨脂酚、补骨脂二氢黄酮甲醚、补骨脂甲素、补骨脂乙素、新补骨脂异黄酮、corylifol A、补骨脂查尔酮、补骨脂定和异补骨脂二氢黄酮9种入血成分体内AUC、Cmax明显升高;补骨脂宁、巴库查尔酮的AUC、Cmax和补骨脂素的AUC有升高的趋势,但差异无统计学意义;补骨脂素的Cmax和异补骨脂素的AUC、Cmax有降低趋势,但差异无统计学意义。以上结果提示,补骨脂多数成分入血暴露水平增加。
      结论 机体患ALD时服用补骨脂,可能导致补骨脂相关肝毒性成分体内暴露量增加,提示补骨脂在ALD患者临床用药时应合理调整剂量。

       

      Abstract:
      OBJECTIVE To investigate the pharmacokinetics of 13 ingredients of Psoraleae Fructus, including psoralen, isopsoralen, bakuchiol, bavachalcone, bavachinin, corylin, psoralidin, bavachin, isobavachalcone, isobavachin, neobavaisoflavone, bakuchalcone and corylifol A in normal rats and alcoholic liver disease(ALD) model rats by ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) technology.
      METHODS A Hypersil GOLD C18 column(2.1 mm×100 mm, 1.9 μm) was employed; the mobile phase was composed of water and acetonitrile with gradient elution; the flow rate was 0.2 mL·min−1; and the column temperature was maintained at 40 ℃. On the basis of the successful establishment of the ALD model in male SD rats, the crude drug solution of Psoraleae Fructus was administered by gavage at a dose of 1.07 g·kg−1. The plasma concentrations of 13 major components were determined by UHPLC-MS/MS, and the pharmacokinetic parameters of each component were calculated using DAS 3.0 software.
      RESULTS  After male SD rats developed ALD and were administered Psoraleae Fructus, the AUC and Cmax of 9 blood-absorbed constituents, namely bakuchiol, bavachinin, bavachin, isobavachalcone, neobavaisoflavone, corylifol A, bavachalcone, psoralidin and isobavachin were significantly increased; the AUC and Cmax of corylin and bakuchalcone, as well as the AUC of psoralen, showed increasing trends, but the differences were not statistically significant; the Cmax of psoralen and the AUC and Cmax of isopsoralen showed decreasing trends, but the differences were not statistically significant. The above results suggested that the systemic exposure levels of most components of Psoralea corylifolia were increased.
      CONCLUSION  When organisms with ALD are administered Psoraleae Fructus, it may lead to an increase in the intake of Psoraleae Fructus-related hepatotoxicity components into the bloodstream, suggesting that the dosage of Psoraleae Fructus should be rationally adjusted during clinical medication for ALD patients.

       

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