Effects of Cryptotanshinone on Cytochrome P450 Isoforms in Rat Liver Microsomes / 中药新药与临床药理

ABSTRACT

Objective To observe the effects of cryptotanshinone (CTS) on cytochrome P450 (CYP) isoforms in the rat liver microsomes. Method The rats were randomized into six groups according to the body weight, 3 rats in each group. CTS groups were treated with CTS at the doses of 20～540 mg/kg per day for 10 days, and the negative control group was treated with 10 mL/kg hydroxylpropyl-β-cyclodextrin solution. The positive group was injected with β-NF(80 mg/kg) intraperitoneally on the 7th day, and all the animals were sacrificed by decapitation on the 10th day after last dose. The liver was got out for the preparation of liver microsomes. The activities of six kinds of CYP isoforms were detected by cocktail in-vitro incubation method. Besides, the expression level of CYP isoforms mRNA and protein in rat liver was analyzed by reverse transcription polymerase chain reaction (RT-PCR) and western-blotting assay, respectively. Results CTS significantly increased the ac-tivity of CYP1A2 in a dose-dependent manner. In CTS groups at the dosages of 20～540 mg/kg, the activity of CYP1A2 was 60 %～430 % higher, CYP1A2 protein expression level was 130 %～320 % higher, and CYP1A2 mRNA expression level was 10 %～150 % higher than that of the negative control group. CTS had no effect on other kinds of CYP isoforms. Conclu-sion CTS can induce hepatic microsome CYP1A2 expression significantly, which indicates potential drug-drug interaction might occurred when CTS is co-administrated with those drugs metabolized by CYP1A2.