The Compatibility Rule Of Si Wu Tang Based On Cytochrome P450Enzyme

Our research focuses on Si Wu Tang(SWT),a decoction of four ingredients,is composed of Radix Rehmanniae, Radix Angelicae Sinensis, Radix PaeoniaeAlba, and Rhizoma Chuanxiong. The aim was to research the effect of SWT andits four ingredients on the cytochrome P450enzyme activity. Microsome of ratliver was prepared after intravenous administration of SWT decoction and thefour ingredients’ decotion. The enzyme activity was quantified by Cocktailmethod, the metabolite was determined by liquid chromatography-massspectrometry(LC-MS/MS).We also researched the combination of SWT’s twoingredients and four SWT’s constituents, fructose (Fru), paeoniflorin (Pae),ferulic acid (FA),tetramethyl pyrazine (TP). Meanwhile, the mRNA expressionof CYP1A2, CYP2B1, CYP2C11and CYP3A1in the liver was detected byreal-time quantitative PCR(Q-PCR).Conclusion: Compared with normal control group, SWT and Pae inducedthe enzyme activities of CYP1A2, rehmanniae-paeoniae, angelicae-paeoniae,angelicae-rhizome, paeoniae-rhizome and TP significantly decreased theactivity of CYP1A2. All groups decreased the activity of CYP2B6.Rehmanniae- paeoniae, angelicae-paeoniae, angelicae-rhizome,paeoniae-rhizome, Fru, FAand TP decreased the activity of CYP2C19. Angelicae-paeoniae, angelicae-rhizome, paeoniae-rhizome induced the activity of CYP2D6, while Fru, Paedecreased the enzyme activities of CYP2D6. Rehmanniae-rhizome decreasedthe activity of CYP3A4, angelicae-rhizome induced the activity of CYP3A4.Some groups have the same effect on the mRNA expression and the enzymeactivities, the change of enzyme acticities maybe was because of the change ofmRNA expression. While the change of enzyme activities in some groups wereinconsistent with the change of mRNAexpression, so the drugs maybe wasdirectly work on the enzyme activity.On the one hand, our research indicate that SWT could inhibit or inducethe CYP450activities and give some reference to drug combination in clinical;on the other hand, the results also indicate that the combination of SWT’s twoingredients can inhibit or induce the CYP450activities but the SWT has nosignificant effect on the CYP450activity, the results proved the classicprescription rationality. Rehmanniae and angelicae play important role in theprescription from the regulation of some enzyme subtype, because its have thesame effect on enzyme activity with SWT decoction.