Effects of crude and vinegar-processed Curcumae Rhizoma on the activities of CYP450 enzymes in rats

Curcumae Rhizoma (CR) has been used in traditional Chinese medicine for thousands of years as an anti-blood stasis and pain-alleviating agent. However, the effects of crude and vinegar-processed Curcumae Rhizoma (VCR) on CYP450 activities are poorly understood. In this study, a “cocktail” method was designed to assess CYP1A2, CYP3A1 and CYP2E1 enzymatic activities in vivo using theophylline, dapsone and chlorzoxazone as probe substrates, based on a developed and validated HPLC method. In addition, real-time RT-PCR was performed to assess CYP1A2, CYP3A1 and CYP2E1 mRNA expression in the rat liver. The results indicated that long-term treatment with the CR extract inhibited CYP1A2 enzymatic activity and induced CYP3A1 activity. Further, VCR inhibited CYP1A2 and CYP2E1 enzymatic activities and induced CYP3A1 activity after administration of both a single dose and multiple doses, and these effects occurred in a time-dependent manner. VCR had greater inhibitory and inducing effects than CR. The mRNA expression results were consistent with the pharmacokinetic results. These results provide a scientific basis for the safe clinical application of CR and VCR in combination with other drugs, potentially preventing possible side effects induced by herb-drug interactions.