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

被引：10

作者：

Hao, Kun ^{[1
]}

Gong, Ping ^{[1
]}

Sun, Shi-Qing ^{[1
]}

Hao, Hai-Ping ^{[1
]}

Wang, Guang-Ji ^{[1
]}

Dai, Yue ^{[2
]}

Chen, Yuan-Cheng ^{[3
]}

Liang, Yan ^{[1
]}

Xie, Lin ^{[1
]}

Li, Fei-Yan ^{[1
]}

Li, Hao-Ye ^{[1
]}

机构：

[1] China Pharmaceut Univ, Key Lab Drug Metab & Pharmacokinet, Nanjing 210009, Peoples R China

[2] China Pharmaceut Univ, Coll Tradit Chinese Mat Med, Nanjing 210009, Peoples R China

[3] Fudan Univ, Huashan Hosp, Inst Antibiot, Shanghai 200433, Peoples R China

来源：

EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES | 2011年 / 44卷 / 1-2期

关键词：

Ginsenoside Rb1; Estradiol; 5-Hydroxytryptamine; Pharmacokinetic-pharmacodynamic model; PHARMACOKINETIC/PHARMACODYNAMIC MODEL; RECEPTOR-BETA; SEROTONIN; ANXIETY; MICRODIALYSIS; VITRO;

D O I：

10.1016/j.ejps.2011.06.014

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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. (C) 2011 Elsevier B.V. All rights reserved.

引用

页码：117 / 126

页数：10

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