Evaluation of the effect of ethanol extracts of antrodia cinnamomea on rat hepatic CYP450 enzyme activity by Cocktail Probe Method
Objective:To investigate the effect of the ethanol extract of antrodia cinnamomea on the activity of rat he-patic microsomal CYP450 subenzymes.Methods:An in vitro metabolic HPLC method was established for rat hepatic mi-crosomes,and the Cocktail probe method was used to evaluate the effect of the ethanol extract of Antrodia cinnamomea on rat hepatic microsomal CYP450 subenzymes.(1)Accurately weighed amounts of metoprolol,omeprazole,phenacetin,chlorzoxazone,tolbutamide,and nifedipine were used to prepare a Cocktail mixed probe substrate solution.(2)Active,in-active,and inhibitor groups were set up.In the active group,rat hepatic microsomes were not inactivated.In the inactive group,rat hepatic microsomes were inactivated,with other steps being the same as in the active group.In the inhibitor groups(quinidine,ticlopidine,α-naphthoflavone,disulfiram,sulfaphenazole,and ketoconazole groups,respectively),inhibitors(2.5 μl each)were added to the active group.The relative activities of CYP2D6,CYP2C19,CYP1A2,CYP2E1,CYP2C9,and CYP3A4/5 subenzymes were detected.Results:Compared with the inactive group,the relative enzyme ac-tivities of CYP2D6,CYP2C19,CYP1A2,CYP2E1,CYP2C9,and CYP3A4/5 were elevated in the active group,with sta-tistically significant differences(P<0.05).Compared with the active group,the relative enzyme activities of CYP1A2 and CYP3A4/5 were reduced in the high,medium,and low dose groups of antrodia cinnamomea,with statistically significant differences(P<0.05).The relative enzyme activity of CYP2C9 was reduced but without statistical significance(P>0.05).The relative enzyme activity of CYP2D6 was reduced in the high and medium dose groups,and the relative enzyme activity of CYP2E1 in the high dose group and that of CYP2C19 in the low dose group were reduced.The relative enzyme activity of CYP2C19 was elevated in the high dose group,all with statistically significant differences(P<0.05).Conclusion:The ethanol extract of antrodia cinnamomea has inhibitory effects on the metabolic activities of CYP1A2,CYP3A4/5,CYP2C9,CYP2D6,and CYP2E1 in rat hepatic microsomes within a certain concentration range,while it has promoting effects on the metabolic activity of CYP2C19 subenzymes within a certain concentration range.
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