RESUMEN
Interaction between foods and drugs is an important consideration in pharmaceutical therapy. Therefore, here, we examined the suppressive effects of the extracts from seven edible herbs on the induction of CYP3A4 gene expression in rifampicin-treated HepG2 cells. We evaluated the structure and suppressive activity of the most effective active compound isolated from dried peppermint (Mentha piperita L.). The structure of the compound was identified as that of pheophorbide a based on spectroscopic data. It suppressed the induction of CYP3A4 mRNA expression by rifampicin in a dose-dependent manner. Quantitative high-performance liquid chromatography showed that 2 g of dry leaves 0.43 mg in one cup of peppermint tea. These findings demonstrate that pheophorbide a suppresses the induction of CYP3A4 mRNA expression in rifampicin-treated HepG2 cells. Pheophorbide is known to cause photosensitivity. However, the effective dose of pheophorbide a that had a suppressive effect was very low, indicating a high safety margin. Abbreviations: DAD: diode array detector; DMEM: Dulbecco's modified Eagle's medium; ELISA: enzyme-linked immunosorbent assay; HPLC: high-performance liquid chromatography; PCR: polymerase chain reaction; PXR: pregnane X receptor; CAR: constitutive androstane receptor; AHR: aryl hydrocarbon receptor; TLC: thin-layer chromatography.
Asunto(s)
Antibióticos Antituberculosos/farmacología , Clorofila/análogos & derivados , Citocromo P-450 CYP3A/genética , Mentha piperita/química , Extractos Vegetales/farmacología , ARN Mensajero/antagonistas & inhibidores , ARN Mensajero/biosíntesis , Rifampin/farmacología , Supervivencia Celular/efectos de los fármacos , Clorofila/química , Clorofila/farmacología , Cromatografía Líquida de Alta Presión , Células Hep G2 , Humanos , Estructura Molecular , Extractos Vegetales/química , Espectroscopía de Protones por Resonancia Magnética , Relación Estructura-ActividadRESUMEN
Two effective cytochrome P450 (CYP) inhibitors were isolated from tarragon, Artemisia dracunculus. Their structures were spectroscopically identified as 2E,4E-undeca-2,4-diene-8,10-diynoic acid isobutylamide (1) and 2E,4E-undeca-2,4-diene-8,10-diynoic acid piperidide (2). Both compounds had dose-dependent inhibitory effects on CYP3A4 activity with IC50 values of 10.0 ± 1.3 µM for compound 1 and 3.3 ± 0.2 µM for compound 2, and exhibited mechanism-based inhibition. This is the first reported isolation of effective CYP inhibitors from tarragon (Artemisia dracunculus) purchased from a Japanese market.
Asunto(s)
Artemisia/química , Inhibidores Enzimáticos del Citocromo P-450 , Inhibidores Enzimáticos/química , Ácidos Grasos Insaturados/química , Piperidinas/química , Extractos Vegetales/química , Sistema Enzimático del Citocromo P-450/química , Inhibidores Enzimáticos/aislamiento & purificación , Ácidos Grasos Insaturados/aislamiento & purificación , Isoenzimas/antagonistas & inhibidores , Isoenzimas/química , Cinética , NADP/química , Piperidinas/aislamiento & purificación , SolucionesRESUMEN
Peanut skin contains large amounts of polyphenols having antiallergic effects. We found that a peanut-skin extract (PSE) inhibits the degranulation induced by antigen stimulation of rat basophilic leukemia (RBL-2H3) cells. A low-molecular-weight fraction from PSE, PSEL, also had inhibitory activity against allergic degranulation. A main polyphenol in PSEL was purified by gel chromatography and fractionated by YMC-gel ODS-AQ 120S50 column. Electrospray ionization mass spectrometry (ESI-MS) analysis of the purified polyphenol gave m/z 599 [M+Na]âº. Based on the results of ¹H-NMR, ¹³C-NMR spectra, and optical rotation analysis, the polyphenol was identified as procyanidin A1. It inhibited the degranulation caused by antigen stimulation at the IC50 of 20.3 µM. Phorbol-12-myristate-13-acetate (PMA) and 2,5,-di(tert-butyl)-1,4-hydroquinone (DTBHQ)-induced processes of degranulation were also inhibited by procyanidin A1. These results indicate that peanut-skin procyanidin A1 inhibits degranulation downstream of protein kinase C activation or Ca²âº influx from an internal store in RBL-2H3 cells.