Abstract
Naringin (NRG) is a common dietary flavonoid in citrus fruits and has been documented to possess multiple pharmacological activities, including anti-oxidant, anti-inflammatory, and neuroprotective effects. Naringin is frequently consumed in combination with common clinical drugs. To date, the effects of NRG on cytochrome P450 enzymes have not been fully investigated yet. In this study, the activities of hepatic CYP1A2, CYP2D2, CYP2C9, CYP2C19, and CYP2E1 in rats after the continuous oral administration of NRG (50 and 500 mg/kg) were evaluated using cocktail probe-drug method. The concentrations of 5 probe drugs (phenacetin, dextromethorphan, diclofenac sodium, omeprazole, and chlorzoxazone) in rat plasma were simultaneously determined with a validated HPLC-MS/MS (high performance liquid chromatography-tandem mass spectrometry) method and then used to calculate corresponding pharmacokinetic parameters. Compared with the control group, the AUC(0- t), AUC(0-∞), t 1/2, and C max of each probe drug in treatment groups showed no significant differences. Meanwhile, fluorescence quantitative polymerase chain reaction (FQ-PCR) analysis revealed that NRG did not significantly affect the mRNA expressions of genes CYP1a2, CYP2d2, CYP2c6, CYP2c11, and CYP2e1 in rat liver. Based on these results, it could be concluded that NRG showed no significant effects on the activities and mRNA expressions of tested CYP450 in rats.
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