In vivo effects of scutellarin on the activities of CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2 by cocktail probe drugs in rats

OBJECTIVE: To investigate the influence of scutellarin on the activities of CYP1A2, CYP2C11, CYP2D1, and CYP3A1/2 in rats in vivo. METHODS: Scutellarin and saline were intravenously administered to male Wistar rats via the caudal vein for 7 days consecutively. On the 8th day, the rats were treated with probe drugs of caffeine (10 mg/kg), tolbutamide (10 mg/kg), metoprolol (20 mg/kg), dapsone (10 mg/kg) by intraperitoneal injection, and the blood samples were collected at different times. The probe drugs in the blood samples were measured by ultra performance liquid chromatography mass spectrometer (UPLC-MS/MS) and the changes of the pharmacokinetics parameters of the drugs were observed to evaluate the effects of scutellarin on the four CYP450 isoforms in rats. RESULTS: The activity of CYP1A2 in rats was inhibited significantly after treatment with scutellarin by increased caffeine t1/2 (21.76%, P < 0.05), T(max) (43.05%, P < 0.05), C(max) (43.92%, P < 0.01) and AUC(0-infinity) (50.88%, P < 0.01) in the scutellarin-treated group compared with those of the blank control. The activity of CYP2C11 in rats was inhibited significantly after treatment with scutellarin by increased tolbutamide t1/2 (16.74%, P < 0.01), T(max) (116.87%, P < 0.05), C(max) (63.78%, P < 0.01) and AUC(0-infinity) (70.61%, P < 0.01) in the scutellarin-treated group compared with those of the blank control. The activity of CYP3A1/2 in rats was inhibited significantly after treatment with scutellarin by increased dapsone t1/2 (45.28%, P < 0.05), T(max) (81.55%, P < 0.05), C(max) (155.58%, P < 0.01)and AUC(0-infinity) (176.35%, P < 0.01) in the scutellarin-treated group compared with those of the blank control. The pharmacokinetic parameters of metoprolol were not significantly changed in the scutellarin-treated group compared with those of the blank control. CONCLUSION: Scutellarin could significantly inhibit CYP1A2, CYP2C11 and CYP3A1/2 activities in rats in vivo, but had no effects on the activity of CYP2D1.