Investigation on P450s involved in emodin`s phaseImetabolism and inhibitory effect of emodin on P450s

AIM:To identify the P450sinvolved in emodin`s phaseⅠmetabolism and inhibitory effect of emodin on the P450s,in order to provide experimental evidence for predicting possible emodin-drug interactions.METHODS:Human liver microsome and recombinant P450enzymes were incubated with emodin and CYP3A4 inhibitor ketoconazole(KTZ)for 20 mins in vitro,emodin concentrations were determined by LC-MS/MS method.Inhibitory effects of emodin on the P450enzyme isoforms were investigated using an established in vitro cocktail incubation approach in our lab.RESULTS:Co-incubation with human liver microsomes and recombinant CYP3A4 system in vitro showed that emodin remains 68.5%and 0.015%of the initial content,100μmol/L KTZ could decrease the elimination rate to 0.1% and 27.7%respectively.The results from the cocktail experiment indicated that emodin had a moderate inhibition on CYP1A2,CYP2C9,CYP2D6with IC50as 3.31,2.60,2.56μmol/L respectively.CONCLUSION:CYP3A4plays a key role for emodin biotransformation in phaseⅠmetabolism,possessing the inhibitory effect on multiple P450s.Attention should be paid to avoid the possible emodin-drug interaction when emodin-containing preparations are prescribed with substrates of these mentioned P450s.