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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 CYP450activities are poorly understood.In this study, a "cocktail" method was designed for assessing CYP1A2, CYP3A4 and CYP2E1 enzymes activities in vivo using theophylline, dapsone and chlorzoxazone as probe substrates based on a developed and validated HPLC method.A real-time RT-PCR method was performed to assess the levels on mRNA expression of CYP1A2, CYP3A4 and CYP2E1 in rat liver in addition.The results indicated that a long-term treatment of CR extract can inhibit CYP1A2 enzyme and induce CYP3A4 enzyme activities.VCR has an effect of inhibiting CYP1A2 and CYP2E1 enzymes and inducing CYP3A4 enzyme activities both after single dose and multiple dose administration and the effect was in a time-dependent manner.The inhibition or induction effect of VCR is stronger than CR.The mRNA expression results were consistent with the pharmacokinetic results.The results provide a scientific data for the safe clinical application of CR and VCR in combination with other drugs, potentially preventing possible side effects induced by herb-drug interactions..