Studies On The Effects Of Xiaochaihu Decoction On The Expression Of Cytochrome P450 Isozymes In Rats

Objective: To study the effect of Xiaochaihu decoction on the gene and protein levels of hepatic cytochrome P450(CYP450)isoforms,providing references for the clinical rational use of combination of Xiaochaihu decoction and related preparations with other drugs.Methods: 120 normal SD male rats were randomly divided according to body weight into three groups corresponding to the duration of administration of 3,6,and 9 days.Each group of rats was further divided into control group(2 m L 5‰ CMC-Na),liver drug enzyme inducer group(50 mg/kg.d rifampicin)and experimental groups(Xiaochaihu decoction: low dose 1.7 g/kg.d,medium dose 3.4 g/kg.d,high dose 6.8 g/kg.d),with 8 rats in each group and the corresponding drugs were administered intragastrically to the rats every morning.After the last dose in each duration of administration,the rats were fasted for 24 h and sacrificed by cervical dislocation and the livers were taken to extract total RNA and total protein.The effects of Xiaochaihu decoction on the CYP450 subtypes CYP1A2,CYP1B1,CYP2C11,CYP2C23,CYP2D6,CYP2E1 and CYP3A1 m RNA and protein expression in rats were evaluated by real-time fluorescence quantitative detection(q RT-PCR)and western blot(WB).Results:(1)Xiaochaihu decoction showed inhibition effect on CYP1A2 gene and protein expression in short-term administration;Xiaochaihu decoction showed induction effect on CYP1A2 gene expression and had no effect on protein expression in prolonged administration time.(2)Xiaochaihu decoction mainly showed no effect on CYP1B1 gene and protein expression during the whole course of administration.(3)Xiaochaihu decoction showed inhibition effect on CYP2C11 gene expression in short-term administration;and showed induction effect on CYP2C11 gene expression in prolonged administration time.Xiaochaihu decoction mainly showed inhibition effect on CYP2C11 protein expression during the whole course of administration.(4)Xiaochaihu decoction showed induction effect on CYP2C23 gene expression in short-term administration;and showed inhibition effect on CYP2C23 gene expression in prolonged administration time.Xiaochaihu decoction mainly showed no effect on CYP2C23 protein expression during the whole course of administration.(5)Xiaochaihu decoction showed induction effect on CYP2D6 gene expression in a certain period of time.Xiaochaihu decoction had no effect on CYP2D6 protein expression during the whole course of administration.(6)Xiaochaihu decoction showed inhibition effect on CYP2E1 gene expression in short-term administration;and showed induction effect on CYP2E1 gene expression in prolonged administration time.Xiaochaihu decoction mainly showed inhibition effect on CYP2E1 protein expression during the whole course of administration.(7)Xiaochaihu decoction showed inhibition effect on CYP3A1 gene expression in short-term administration;and showed induction effect on CYP3A1 gene expression in prolonged administration time.Xiaochaihu decoction mainly showed induction effect on CYP3A1 protein expression during the whole course of administration.Conclusion:During the whole course of administration(3-9 days),Xiaochaihu decoction showed inhibition/induction effect on gene expression of CYP1A2,CYP2C11,CYP2C23,CYP2E1,CYP3A1;and showed induction effect on gene expression of CYP2D6;and showed no effect on gene expression of CYP1B1.During the whole course of administration(3-9days),Xiaochaihu decoction mainly showed no effect on protein expression of CYP1A2,CYP1B1,CYP2C23,CYP2D6;and showed inhibition effect on protein expression of CYP2C11,CYP2E1;and showed induction effect on protein expression of CYP3A1.When Xiaochaihu decoction is combined with different substrate drugs of different subtypes of CYP,it should be considered that different drug interactions may occur at different courses of treatment and/or doses.