Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, P. R. China.
J Sep Sci. 2022 Jul;45(13):2228-2238. doi: 10.1002/jssc.202101019. Epub 2022 May 3.
Zingiberis Rhizoma and Ginseng Radix et Rhizoma are usually used together for the treatment of ulcerative colitis in clinical practices. However, their compatibility mechanism remains unclear. In this study, a rapid and sensitive liquid chromatography with tandem mass spectrometry method was developed for simultaneous quantification of ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, and 6-gingerol in rat plasma after oral administration of Zingiberis Rhizoma-Ginseng Radix et Rhizoma herb pair and its single herb extracts. The calibration curves exhibited good linearity, with correlation coefficients of more than 0.993. The precision deviations of intra- and interday analysis were within 10.66%, and accuracy error ranged from -12.74 to 11.56%. The average recoveries of analytes were higher than 76.60% and the matrix effects were minimal. Thus, the validated method was successfully applied to a pharmacokinetic study of four ingredients in normal and ulcerative colitis rat plasma. The results indicated that the pharmacokinetic parameters of four analytes in normal and model groups showed significant differences. The larger exposure (the mean AUC of ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, and 6-gingerol were increased by 50.93, 141.90, 3.68, and 37.25%, respectively) and slower elimination (the CLz/F of ginsenoside Re, ginsenoside Rg1, and 6-gingerol were decreased by 52.94, 83.64, and 32.18%, respectively) were observed in ulcerative colitis rats. Furthermore, compared with single herbs, the analytes in rat plasma after oral administration of combined extracts presented relatively high systemic exposure levels with AUC > 2000 h·ng/mL and C > 200 ng/mL. Collectively, the differences of pharmacokinetic characteristics revealed the synergistic effect of Zingiberis Rhizoma-Ginseng Radix et Rhizoma herb pair, which provided a valuable and reliable basis for its clinical application in the treatment of ulcerative colitis.
干姜和人参通常在临床上联合用于治疗溃疡性结肠炎。然而，其配伍机制尚不清楚。本研究建立了一种同时测定大鼠灌胃干姜-人参药对对及单味药提取物后血浆中人参皂苷 Re、人参皂苷 Rg1、人参皂苷 Rb1 和 6-姜辣素的液相色谱-串联质谱分析方法。方法学考察结果表明，该方法线性关系良好，相关系数均大于 0.993；日内和日间精密度偏差均小于 10.66%，准确度误差在-12.74%至 11.56%之间；各分析物的平均回收率均高于 76.60%，基质效应较小。因此，该方法成功应用于正常和溃疡性结肠炎大鼠血浆中 4 种成分的药代动力学研究。结果表明，正常和模型组大鼠血浆中 4 种分析物的药代动力学参数均有显著差异。与正常组相比，模型组大鼠中 4 种分析物的暴露量（人参皂苷 Re、人参皂苷 Rg1、人参皂苷 Rb1 和 6-姜辣素的 AUC 分别增加了 50.93%、141.90%、3.68%和 37.25%）增大，消除速度（人参皂苷 Re、人参皂苷 Rg1 和 6-姜辣素的 CLz/F 分别降低了 52.94%、83.64%和 32.18%）减慢。此外，与单味药相比，药对对大鼠灌胃后，4 种分析物在血浆中的系统暴露水平相对较高，AUC > 2000 h·ng/mL，C > 200 ng/mL。综上所述，药对对药代动力学特征的差异揭示了干姜-人参药对的协同作用，为其在溃疡性结肠炎治疗中的临床应用提供了有价值的可靠依据。
