Mechanism-based pharmacokinetic-pharmacodynamic modeling of the estrogen-like effect of ginsenoside Rb1 on neural 5-HT in ovariectomized mice

作者：Hao, Kun; Gong, Ping; Sun, Shi-Qing; Hao, Hai-Ping; Wang, Guang-Ji^*; Dai, Yue; Chen, Yuan-Cheng; Liang, Yan; Xie, Lin; Li, Fei-Yan; Li, Hao-Ye

来源：European Journal of Pharmaceutical Sciences, 2011, 44(1-2): 117-126.

DOI：10.1016/j.ejps.2011.06.014

• Ginsenoside Rb1
• Estradiol
• 5-Hydroxytryptamine
• Pharmacokinetic-pharmacodynamic model

We sought to develop a mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) model to characterize the effects of ginsenoside Rb1 (Rb1) and estradiol (E-2) on neural 5-hydroxytryptamine (5-HT) concentration in ovariectomized mice.
PK data of Rb1 and E-2 were obtained in plasma and brain. Brain levels of 5-HT, tryptophan (TRP), 5-hydroxytryptophan (5-HTP), and 5-hydroxyindoleacetic acid (5-HIAA) were determined after a single intravenous injection of Rb1 (20 mg/kg) and E-2 (0.2 mg/kg) in ovariectomized mice. The activities of tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AAAD), and monoamine oxidase (MAO) were also evaluated.
Rb1 and E-2 elevated neural 5-HT levels via TPH activation and MAO inhibition, respectively. Effects were well described by the mechanism-based PK-PD model. The net effect of increased 5-HT induced by MAO inhibition is greater than TPH activation.
The increased brain levels of 5-HT induced by Rb1 and E-2 were well described by the present PK-PD model, suggesting the use and further development of this mechanism-based model for the effects of ginsenoside on brain 5-HT levels.

• 出版日期2011-9-18
• 单位中国药科大学; 复旦大学