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1.
Chin J Nat Med ; 14(7): 534-40, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27507204

RESUMEN

Glycyrrhizin is a major bioactive component of liquorice, which exerts multiple biochemical and pharmacological activities and is frequently used in combination with other drugs in the clinic. Mycophenolate mofetil (MMF), an immunosuppressant widely used in transplant patients, is metabolized by UDP-glucuronyltransferases (UGTs). Although significant evidence supports that glycyrrhizin could interact with the cytochrome P450s (CYPs), few studies have addressed its effects on UGTs. The present study aimed at investigating the regulatory effects of diammonium glycyrrhizinate (GLN) on UGTs in vitro and in vivo. We found that long-term administration of GLN in rats induced overall metabolism of MMF, which might be due to the induction of UGT1A protein expression. Hepatic UGT1A activity and UGT1A mRNA and protein expression were significantly increased in GLN-treated rats. UGT1A expression levels were also increased in the intestine, contradicting with the observed decrease in intestinal UGT1A activities. This phenomenon may be attributed to different concentrations of glycyrrhetinic acid (GA) in liver and intestine and the inhibitory effects of GA on UGT1A activity. In conclusion, our study revealed that GLN had multiple effects on the expression and activities of UGT1A isoforms, providing a basis for a better understanding of interactions between GLN and other drugs.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Glucuronosiltransferasa/química , Ácido Glicirrínico/farmacología , Interacciones de Hierba-Droga , Intestinos/enzimología , Hígado/enzimología , Animales , Medicamentos Herbarios Chinos/química , Glucuronosiltransferasa/metabolismo , Ácido Glicirrínico/química , Intestinos/química , Intestinos/efectos de los fármacos , Cinética , Hígado/química , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley
2.
Chin J Nat Med ; 11(5): 560-5, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24359784

RESUMEN

AIM: To identify and quantify the major metabolites of salvianolic acid B (SAB) after intravenous injection in rats. METHODS: LC-IT/TOF-MS was used to identify the metabolites in rat bile, plasma, and urine; LC-MS/MS was used to quantify the two major metabolites. RESULTS: In rat bile, plasma, and urine, nine metabolites were identified, including methylated metabolites of SAB, lithospermic acid (LSA), the decarboxylation and methylation metabolites of LSA, salvianolic acid S (SAS), and dehydrated-SAS. The t1/2 of monomethyl-SAB and LSA were both very short, and monomethyl-SAB had a larger AUC than LSA in rats. CONCLUSION: Nine metabolites were found, the metabolic pathway was described, and the pharmacokinetic profiles of LSA and monomethyl-SAB were studied, thereby clarifying that methylation was the dominant metabolic pathway for SAB in rats.


Asunto(s)
Benzofuranos/metabolismo , Benzofuranos/farmacocinética , Administración Intravenosa , Animales , Benzofuranos/administración & dosificación , Benzofuranos/química , Bilis/química , Masculino , Estructura Molecular , Plasma/química , Ratas , Ratas Sprague-Dawley , Orina/química
3.
Chin J Nat Med ; 11(3): 309-13, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23725847

RESUMEN

AIM: This study was designed to explore the effects of short-term and long-term pretreatment of diammonium glycyrrhizinate (GLN) on the pharmacokinetics of entecavir (ETV) in rats. METHODS: Male SD rats were randomized into short-term and long-term experimental groups, respectively. In the short-term experiment, the control group received saline, the low dose group received GLN 13.5 mg·kg(-1) and the high dose group received GLN 40.5 mg·kg(-1). ETV (0.09 mg·kg(-1)) was given i.g. 0.5 h after saline/GLN administration. For the long-term experiment, rats were allocated into two experimental designs. The control group received saline/ETV (0.09 mg·kg(-1)), the low dose group received GLN 13.5 mg·kg(-1)/ETV 0.09 mg·kg(-1) + GLN 13.5 mg·kg(-1), while the high dose group received GLN 40.5 mg·kg(-1)/ETV 0.09 mg·kg(-1) + GLN 40.5 mg·kg(-1); all administration was continued for 15 days. On the 16(th) day, 0.09 mg·kg(-1) ETV was administrated to all groups. Blood samples were obtained at different time points after ETV administration to determine plasma ETV concentrations. RESULTS: Pretreatment with glycyrrhizin resulted in no significant alterations in the main pharmacokinetic parameters of ETV in the short-term and long-term administration experiments. CONCLUSION: Diammonium glycyrrhizinate has no effect on ETV pharmacokinetics in rats.


Asunto(s)
Ácido Glicirrínico/farmacología , Guanina/análogos & derivados , Animales , Interacciones Farmacológicas , Guanina/sangre , Guanina/farmacocinética , Masculino , Ratas , Ratas Sprague-Dawley
4.
Eur J Pharm Sci ; 44(1-2): 117-26, 2011 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-21740969

RESUMEN

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.


Asunto(s)
Encéfalo/efectos de los fármacos , Ginsenósidos , Modelos Biológicos , Neuronas/efectos de los fármacos , Fitoestrógenos , Serotonina/metabolismo , 5-Hidroxitriptófano/metabolismo , Animales , Encéfalo/enzimología , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Estradiol/sangre , Estradiol/farmacocinética , Estradiol/farmacología , Femenino , Ginsenósidos/farmacocinética , Ginsenósidos/farmacología , Indoles/metabolismo , Ratones , Ratones Endogámicos , Neuronas/enzimología , Neuronas/metabolismo , Ovariectomía , Fitoestrógenos/farmacocinética , Fitoestrógenos/farmacología , Factores de Tiempo
5.
Eur J Pharmacol ; 659(1): 15-25, 2011 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-21414307

RESUMEN

Decreased 5-hydroxytryptamine (5-HT) concentration in the brain has been linked to central nervous system dysfunctions, especially in menopausal women. Ginsenoside Rb1, a potential phytoestrogen, has been shown to improve central nervous system dysfunctions, comparable to the estrogen treatment. To investigate the estrogen-like effects of ginsenoside Rb1 on neural 5-HT disposition and behavioral tasks, we quantified the concentrations of 5-HT and other related endogenous substances in the frontal cortex and striatum of ovariectomized mice. The activities of tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AAAD) and monoamine oxidase (MAO) were also measured to evaluate the synthesis and metabolism of neural 5-HT. Our work shows that both ginsenoside Rb1 and estradiol increased the neural 5-HT concentration. Ginsenoside Rb1 and estradiol administration resulted in elevated TPH and depressed MAO activities, indicating that modulating the synthesis and metabolism of neural 5-HT successfully elevated 5-HT concentration. Ginsenoside Rb1 and estradiol also improved object recognition and decreased immobility time in the forced swimming test. However, a pretreatment with clomiphene (an estrogen receptor antagonist) blocked the beneficial effects of ginsenoside Rb1 and estradiol, suggesting that the estrogen-like effects of ginsenoside Rb1 were estrogen receptor-dependent.


Asunto(s)
Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Estrógenos/farmacología , Ginsenósidos/farmacología , Panax/química , Serotonina/metabolismo , Animales , Encéfalo/enzimología , Encéfalo/fisiología , Clomifeno/farmacología , Estradiol/farmacología , Femenino , Ratones , Actividad Motora/efectos de los fármacos , Neurotransmisores/metabolismo , Ovariectomía/efectos adversos , Reconocimiento en Psicología/efectos de los fármacos , Natación , Factores de Tiempo
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