Zhang Xueju, Wang Lu, Zheng Zhong, Pi Zifeng, Liu Zhiqiang, Song Fengrui
National Center of Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China; University of Chinese Academy of Sciences, Beijing 100039, China.
National Center of Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
J Pharm Biomed Anal. 2017 Jun 5;140:146-154. doi: 10.1016/j.jpba.2017.03.040. Epub 2017 Mar 21.
Iridoid glycosides consist the main bioactive constituents of Gardenia jasminoides Ellis (G. jasminoides), which is used alone or in combination with other medicine herbs for treatment of diabetes mellitus in China. This paper investigated for the first time comparative pharmacokinetics (PKs) of four unbound iridoids (including genipin, geniposide, gardenoside and geniposidic acid) in rat blood between healthy and type 2 diabetic groups with different disease progressions (9 or 13 weeks). Online microdialysis-ultra performance liquid chromatography-mass spectrometry (MD- UPLC-MS/MS) method was used after oral administration of iridoid extracts obtained from the fruits of G. jasminoides. Student's t-test was used for statistical comparison of PK parameters. Results showed that genipin, geniposide and geniposidic acid feature higher C, larger area under the curve (AUC), lower clearance (CL), longer T and mean residence time (MRT) in type 2 diabetic rats than those in healthy rats (p<0.05). However, no significant difference was observed in PK parameters between the two diabetic groups with different complication progressions (p>0.05). Type 2 diabetic rats showed significantly altered PK behaviors of genipin, geniposide and geniposidic acid (especially systemic exposure, AUCs of genipin, geniposide and geniposidic acid). Online MD-UPLC-MS/MS provides real-time sampling and monitoring, these functions can be applied to PKs of iridoids from G. jasminoides.
环烯醚萜苷是栀子的主要生物活性成分，在中国，栀子单独或与其他草药联合用于治疗糖尿病。本文首次研究了健康组和2型糖尿病组（病程分别为9周或13周）大鼠血液中四种游离环烯醚萜（包括京尼平、栀子苷、栀子苷元和京尼平苷酸）的比较药代动力学。口服栀子果实提取物后，采用在线微透析-超高效液相色谱-质谱联用（MD-UPLC-MS/MS）法。采用Student's t检验对药代动力学参数进行统计学比较。结果表明，与健康大鼠相比，2型糖尿病大鼠中京尼平、栀子苷和京尼平苷酸的C更高、曲线下面积（AUC）更大、清除率（CL）更低、半衰期（T）和平均驻留时间（MRT）更长（p<0.05）。然而，在两个并发症进展不同的糖尿病组之间，药代动力学参数没有观察到显著差异（p>0.05）。2型糖尿病大鼠显示出京尼平、栀子苷和京尼平苷酸的药代动力学行为发生了显著改变（尤其是全身暴露，京尼平、栀子苷和京尼平苷酸的AUC）。在线MD-UPLC-MS/MS提供实时采样和监测，这些功能可应用于栀子中环烯醚萜的药代动力学研究。
