The Regulation Of Wenglitong On MRNA And Protein Expression Of Cytochrome P450 Isoenzymes In Rat Liver

Objective: Wenglitong has good effect in treating prostatic hyperplasia, chronic prostatitis and chronic nonbacterial prostatitis, which is a kind of pure compound traditional Chinese medicine in our country. Currently, wenglitong capsule are always combined with western medicine for treatment of prostate disease in the clinical. Patients suffered from prostate diseases are often associated with cardiovascular diseases or other diseases. The combination of traditional Chinese medicine with western medicine may lead to drug-drug interactions. Cytochrome P450(CYP) enzymes are primarily responsible for drug metabolism. In addition, induction and inhibition of CYP enzymes have closely involved in pharmacokinetic drug-drug interaction. However, the effects of wenglitong capsule on CYP enzymes have not been reported. In this study, we investigated the effects of long-term intragastric administration of wenglitong capsule on the m RNA and protein expression levels of CYP enzymes in the rat.Methods: Sixteen healthy male SD rats, weighting 180-200 g, were randomly divided into control group and wenglitong(WLT) group. The control group was intragastrically administered by 0.5% sodium carboxymethyl cellulose(CMC-Na) solution and the wenlitong group was intragastrically administered by wenglitong at the dosage of 205.7 mg/kg(5 times higher than the therapentic dosage). The wenglitong suspension was preparaed by 0.5% CMC-Na solution. After intragastric administration of wenglitong for two months, the rats were killed on the next day after the last administration of drug. The liver was perfused with normal saline and turned into muddy color by in situ brain perfusion technique, then quickly excised liver tissue kept into cryopreservation tubes. Samples were stored at-80℃ for later use. The m RNA expression level of CYP1A2, CYP2B1, CYP2C11, CYP2D1, CYP2E1, CYP3A1 and CYP3A2 subtypes were investigated by Real-time PCR technique and the protein expression level of CYP1A1, CYP1A2, CYP2C11, CYP2D1, CYP2E1 and CYP3A1 subtypes were observed by Western-blot technique.Results:1 The effects of wenglitong on m RNA expression of different CYP450 subtypes in rat liver.Compared with the control group, the m RNA expression levels of CYP2B1, CYP2C11 and CYP3A2 were increased significantly after intragastric administration of wenglitong for two months in rat liver of the wenlitong group(P<0.01). The m RNA relative expression of CYP2B1, CYP2C11 and CYP3A2 were 1.59±0.09 、 1.28±0.04 and 1.39±0.05 respectively in rat liver of the wenlitong group.Compared with the control group, the m RNA expression levels of CYP1A2 and CYP3A1 were increased, but there was no significant difference(P>0.05).The m RNA relative expression of CYP1A2 and CYP3A1 were 1.33±0.08 and 1.23±0.12 respectively in rat liver of the wenlitong group.Compared with the control group, the m RNA expression levels of CYP2D1 and CYP2E1 did not show the significant difference(P>0.05). The m RNA relative expression of CYP2D1 and CYP2E1 were 1.07±0.03 and 1.01±0.04 respectively in rat liver of the wenlitong group.2 The effects of wenglitong on protein expression of CYP subtypes in rat liver.After intragastric administration of wenglitong for two months, the protein expression level of CYP1A2 was increased significantly in rat liver of wenlitong group compared with the control group(P<0.01). The ratios of CYP1A2 to GAPDH in the wenlitong group and control group were 0.58±0.04 and 0.41±0.01 respectively.Compared with the control group, the protein expression levels of CYP1A1, CYP3A1 and CYP2D1 were decreased significantly in rat liver of wenlitong group(P<0.01). The ratios of CYP1A1, CYP3A1 and CYP2D1 to GAPDH were 0.24±0.01, 0.36±0.02 and 1.38±0.01 in the wenlitong group and 0.32±0.02, 0.44±0.01, 1.56±0.02 in the control group.Compared with the control group, the protein expression levels of CYP2C11 and CYP2E1 did not show the significant difference(P>0.05) in wenlitong group. The ratios of CYP2C11 and CYP2E1 to GAPDH were 1.10±0.02 and 0.26±0.01 in the wenglitong group and 1.08±0.05 and 0.24±0.01 in the control group.Conclusions:1 The m RNA expression levels of CYP2B1, CYP2C11 and CYP3A2 were increased significantly in rat liver after intragastric administration of wenglitong for two months.2 The protein expression levels of CYP1A2 was increased significantly and the protein expression level of CYP1A1, CYP3A1 and CYP2D1 were decreased significantly in rat liver after intragastric administration of Wenglitong for two months.