Objective: Taking primary rat hepatocytes (PRH) model

to explore the effect of Fuzheng Huayu recipe (FZHY) on rat cytochrome P450 enzyme (CYP450). Method: PRH were isolated and cultured by two-step perfusion method.With the formation of the hepatic plate structure

FZHY was added to culture for 24 h

then replaced with culture medium containing specific probe substrates of CYP450 (phenacetin-CYP1A2

tolbutamide-CYP2C9

dextromethorphan hydrobromide-CYP2D6

testosterone-CYP3A4)

the supernatant was aspirated after 2 h

the corresponding products of the probe drugs were detected by UPLC-MS/MS. Result: CYP1A2

CYP2C9

CYP2D6 and CYP3A4 in PRH had good metabolic activity.The probe drugs had no toxicity on PRH in the range of 0-500 μmol · L-1

FZHY had no toxicity on PRH in the range of 0.5-500 μg · L-1.FZHY could slightly protect PRH with concentration of 5 μg · L-1.After PRH was cultured with 5 μg · L-1 FZHY for 24 h

Michaelis constant (Km) of tolbutamide decreased by 20.8%

Km of dextromethorphan hydrobromide decreased by 39.2%

Km of phenacetin decreased by 17.4%

Km of testosterone decreased significantly. Conclusion: FZHY can inhibit the activity of CYP1A2

CYP2C9

CYP2D6 and CYP3A4 in PRH.