Effects of Xiaochaihu decoction on the expression of cytochrome P450s in rats

Abstract

Xiaochaihu decoction is one of the most important traditional Chinese medicines that is widely used with other drugs in clinical practice, and may cause drug-drug interactions. However, there is not sufficient experimental evidence for the effects of Xiaochaihu decoction on cytochrome P450s (CYPs). The aim of the present study was to investigate the effects of Xiaochaihu decoction on the mRNA and protein levels of hepatic CYPs. Eighty normal male Sprague-Dawley (SD) rats were randomly divided into two groups based on body weight and duration of drug administration (3 and 6 days). Each group was further divided into subgroups: Control group (2 ml 5‰ CMC-Na); hepatic enzyme inducer group (50 mg/kg/day rifampicin); and experimental groups (Xiaochaihu decoction: Low dose, 1.7 g/kg/day; medium dose, 3.4 g/kg/day; high dose, 6.8 g/kg/day). The effects of Xiaochaihu decoction on Cyp1a2, Cyp3a1, Cyp2d6, and Cyp1b1 mRNA and protein expression in rats were evaluated using reverse transcription quantitative reverse transcription polymerase chain reaction and western blot analysis. After 3 days, medium dose of Xiaochaihu decoction inhibited the mRNA and protein expression of Cyp1a2, Cyp3a1 and Cyp1b1. In addition, after 6 days, Xiaochaihu decoction induced Cyp3a1 mRNA expression at low and medium doses; Cyp2d6 mRNA expression at low and high doses; and Cyp2d6 protein expression at high doses. Nonetheless, the gene and protein expression of Cyp1b1 was not affected at any dose. The findings of the present study may provide insights into potential drug-drug interactions associated with Xiaochaihu decoction.

Keywords: Xiaochaihu decoction; cytochrome P450; drug metabolism; drug-drug interaction; traditional Chinese medicines.

Figure 1

HPLC chromatogram of baicalin. Representative HPLC chromatogram of baicalin reference substance (A) and baicalin in Xiaochaihu decoction (B), with a retention time of 4.87 and 4.85 min, respectively. HPLC, high-performance liquid chromatography.

Figure 2

Relative expression level of Cyp1a2 mRNA and protein level. The relative expression level of Cyp1a2 mRNA (A) and protein (B) in the liver of rats which were treated with Xiaochaihu decoction once daily for 3 and 6 days. The data are expressed as mean ± SE (n=8). ^*P<0.05; ^**P<0.01 vs. control. C, control; R, rifampicin; L, low-dose; M, medium-dose; and H, high-dose group.

Figure 3

Relative expression level of Cyp3a1 mRNA and protein. Relative expression level of Cyp3a1 mRNA (A) and protein (B) in the liver of rats that were treated with Xiaochaihu decoction once daily for 3 and 6 days. The data are expressed as mean ± SE (n=8). ^*P<0.05; ^**P<0.01 vs. control rats; ^#P<0.05; ^##P<0.01 vs. Xiaochaihu decoction low-dose group; ^$$P<0.01 vs. Xiaochaihu decoction medium-dose group rats. C, control; R, rifampicin; L, low-dose; M, medium-dose; and H, high-dose group.

Figure 4

Relative expression level of Cyp2d6 mRNA and protein. The relative expression level of Cyp2d6 mRNA (A) and protein (B) in the liver of rats that were treated with Xiaochaihu decoction once daily for 3 and 6 days. The data are expressed as the mean ± SE (n=8). ^*P<0.05; ^**P<0.01 vs. control. C, control; R, rifampicin; L, low-dose; M, medium-dose; and H, high-dose group.

Figure 5

Relative expression level of Cyp1b1 mRNA and protein. The relative expression level of Cyp1b1 mRNA (A) and protein (B) in the liver of rats that were treated with Xiaochaihu decoction once daily for 3 and 6 days. The data are expressed as the mean ± SE (n=8). ^*P<0.05 vs. control. C, control; R, rifampicin; L, low-dose; M, medium-dose; and H, high-dose group.