Effects of paeoniflorin on the activities and mRNA expression of rat CYP1A2, CYP2C11 and CYP3A1 enzymes in vivo

Abstract

1. Paeoniflorin is the major constituent in extracts of the peony root, the purpose of the present study was to assess the effects of paeoniflorin on the activities and mRNA expression of the rat hepatic drug-metabolizing enzymes cytochrome P450 (CYP1A2), CYP2C11 and CYP3A1 in vivo. 2. Sprague-Dawley (SD) male rats were treated with paeoniflorin at the dosage of 25, 50 and 100 mg/kg or 0.9% sodium chloride solution by intragastric administration for 7 days, then were given probe drugs phenacetin (CYP1A2), tolbutamide (CYP2C11), or midazolam (CYP3A1) orally on the eighth day. Blood samples were collected at various times, and the plasma concentrations of the probe drugs were estimated with ultra-high-performance liquid chromatography. The mRNA expression levels of rat hepatic CYP1A2, CYP2C11 and CYP3A1 were analyzed with real-time PCR. 3. The pharmacokinetic results indicated that paeoniflorin inhibits the activities of CYP1A2, CYP2C11 and CYP3A1 in vivo. The effect was most pronounced on CYP3A1, according to the United States Food and Drug Administration classification of inhibitors of CYP3A, it reached the category of moderate inhibition. The mRNA expression levels of 3 CYP enzymes were also tended to be inhibited. 4. We conclude that paeoniflorin can inhibit the activities of CYP1A2, CYP2C11 and CYP3A1 in vivo, which may affect the metabolism of drugs that are primarily dependent on these pathways.

Effects of anemoside B4 on pharmacokinetics of florfenicol and mRNA expression of CXR, MDR1, CYP3A37 and UGT1E in broilers

“…UHPLC was performed on UltiMate 3000 HPLC (Thermo Fisher Scientific Inc., Chelmsford, MA, U.S.A) as previously reported [16]. Florfenicol and chloramphenicol were simultaneously determined with a Diamonsil C18 column The LOQ and LOD of florfenicol were validated at 0.05 and 0.02 μg/ml, respectively.…”

“…Total RNA from each sample was isolated by use of TRIzol reagent (Invitrogen Corporation and Applied Biosystems, Inc., Calsbad, CA, USA) according to the manufacturer's protocol. Concentration, purity and integrity of the total RNA samples were measured according to our previous work [16]. RNA samples (800 ng) were reverse transcribed to cDNA with RevertAid Premium Reverse Transcriptase (Thermo Fisher Scientific Inc.) according to the manufacturer's protocol, using C100 PCR (Bio-Rad Laboratories, Inc., Hercules, CA, U.S.A; 2015).…”

Borneol influences the pharmacokinetics of florfenicol through regulation of cytochrome P450 1A2 (CYP1A2), CYP2C11, CYP3A1, and multidrug resistance 1 (MDR1) mRNA expression levels in rats

“…UHPLC analyses were performed using an UltiMate 3000 HPLC (Thermo Fisher Scientific Inc., Chelmsford, MA, USA) as previously described [13]. A Diamonsil C18 column (4.6 mm × 250 mm, 5 μm; Thermo Fisher Scientific Inc.) was used to simultaneously detect florfenicol and chloramphenicol at a constant temperature of 40 °C.…”

Clinical Evaluation of Acetaminophen–Galgeuntang Interaction Based on Population Approaches

“…GGT with five major ingredients also possesses chance of drug interactions when co-administering with other drugs. A number of in vitro studies investigated the influence of GGT and GGT components on cytochrome (CYP) 450 and predicted its drug interactions [7][8][9][10][11][12][13][14][15][16][17][18][19]. For example, GGT reportedly inhibits CYP2C19, CYP2D6, and CYP2E1 [16].…”

“…For example, GGT reportedly inhibits CYP2C19, CYP2D6, and CYP2E1 [16]. Glycyrrhetic acid completely inhibits CYP3A4 [12], and paeoniflorin inhibits the activity of CYP1A2 in vivo [17]. Wu et al [8] reported that ephedrine induces CYP1A2 activity.…”