RESUMEN
Gypenoside LVI, one of the major bioactive triterpene saponins in Gynostemma pentaphyllum, has been regarded as a potential and promising lead drug for anti-tumor strategy. To better understand the pharmacological activities of the component, an investigation of its in vivo metabolism is important and necessary. In the present study, a liquid chromatography-ion trap time of flight tandem mass spectrometry has been utilized to discover and identify the metabolites of gypenoside LVI in rat urine after oral and intravenous administration. Negative electrospray ionisation mass spectrometry was used to discern gypenoside LVI and its possible metabolites in urine samples. As a result, after oral and intravenous administration, eight and six metabolites together with gypenoside LVI were detected and identified in rat urine, respectively. As metabolites of gypenoside LVI, they have never been reported before. Deglycosylation and dehydration were found to be the major metabolic processes of gypenoside LVI in rat.
Asunto(s)
Antineoplásicos Fitogénicos/farmacocinética , Administración Oral , Animales , Antineoplásicos Fitogénicos/administración & dosificación , Biotransformación , Cromatografía Líquida de Alta Presión , Glicosilación , Gynostemma/química , Inyecciones Intravenosas , Masculino , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacocinética , Ratas , Ratas Sprague-Dawley , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en TándemRESUMEN
Folk drug Gynostemma pentaphyllum (Thunb.) Makino contains many biologically active phytochemicals which have been demonstrated to be effective against chronic diseases. As in vivo anti-tumor experiments of G. pentaphyllum extract (GP) show much stronger antitumor activities than in vitro, it is important and necessary to understand the metabolic study of GP. A sensitive and specific U-HPLC-MS method was utilized for the first time to rapidly identify gypenosides and its possible metabolites in rat serum, urine, and faeces after oral administration. Solid phase extraction was utilized in the sample preparation. Negative Electrospray ionisation (ESI) mass spectrometry was used to discern gypenosides and its possible metabolites in rat samples. As a result, after oral administration, a total of seven metabolites of G. pentaphyllum extract were assigned, two from the rat serum and seven both from the rat urine and faeces. As metabolites of G. pentaphyllum extract, all of them have never been reported before.
Asunto(s)
Gynostemma/química , Metabolómica/métodos , Administración Oral , Animales , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/metabolismo , Heces/química , Gynostemma/metabolismo , Límite de Detección , Modelos Lineales , Masculino , Espectrometría de Masas , Extractos Vegetales/administración & dosificación , Extractos Vegetales/análisis , Extractos Vegetales/química , Extractos Vegetales/metabolismo , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los ResultadosRESUMEN
The activity of gypenosides and gynogenin of Gynostemma pentaphyllum against non-small cell lung carcinoma (NSCLC) A549 cells was investigated to identify the structural characteristics of gypenosides and gynogenin to have anti-NSCLC activity. Of the tested dammarane-type compounds, 20S-dammar-24-en-2α,3ß,12ß,20-tetrol showed the strongest activity against A549 cells. Based on the structure and cytotoxic activity relationships of gypenosides and gynogenin, the OH group in C-2, the connected sugar number and the configuration in C-20 were important for cytotoxic activity against A549 cells.
Asunto(s)
Antineoplásicos/farmacología , Gynostemma/química , Triterpenos/farmacología , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Conformación Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Relación Estructura-Actividad , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
OBJECTIVE: To investigate the regulatory effect of Chinese traditional medicine mixture (CTMM) on inflammatory response in rats with severe burn. METHODS: One hundred and ten rats were randomly divided into 3 groups:scalded rats inflicted by 30% III degree scald were treated with CTMM and SD-Ag (CTMM group), scalded rats inflicted by 30% III degree scald were treated with SD-Ag alone (scalded group), and healthy rats were treated with SD-Ag (normal group). The serum contents of TNF-alpha, IL-beta, IL-6, IL-8, IL-4, and IL-10 in rats in the 3 groups were dynamically monitored. RESULTS: The serum contents of TNF-alpha, IL-1beta, IL-6, IL-8, IL4, and IL-10 evidently increased in both the CTMM and scalded groups. But the contents of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, and IL-8) in the CTMM group were much lower than those in the scalded group. However, the contents of anti-inflammatory cytokines (IL-4 and IL-10) in the CTMM group were much higher than those in the scalded group. CONCLUSION: CTMM has double-way regulatory effect on the inflammatory response in rats with severe burn.