title: Mechanism-based pharmacokinetic-pharmacodynamic modeling of the estrogen-like effect of ginsenoside Rb1 on neural 5-HT in ovariectomized mice.
abstract: 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 (20mg/kg) and E(2) (0.2mg/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.
authors: Key Lab of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing, PR China.
authors: Kun
authors: K
authors: Hao
authors: Ping
authors: P
authors: Gong
authors: Shi-Qing
authors: SQ
authors: Sun
authors: Hai-Ping
authors: HP
authors: Hao
authors: Guang-Ji
authors: GJ
authors: Wang
authors: Yue
authors: Y
authors: Dai
authors: Yuan-Cheng
authors: YC
authors: Chen
authors: Yan
authors: Y
authors: Liang
authors: Lin
authors: L
authors: Xie
authors: Fei-Yan
authors: FY
authors: Li
authors: Hao-Ye
authors: HY
authors: Li
mesh_terms: D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D036145:Ginsenosides / Q000493:pharmacokinetics / Q000494:pharmacology; D007211:Indoles / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010052:Ovariectomy; D048789:Phytoestrogens / Q000493:pharmacokinetics / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors
chemical_list: D036145:Ginsenosides; D007211:Indoles; D048789:Phytoestrogens; D012701:Serotonin; D004958:Estradiol; C024139:indole-3-lactic acid; C442759:ginsenoside Rb1; D006916:5-Hydroxytryptophan