The Effect Of Celery Extract On Cytochrome P4502A6

Cytochrome P450(CYP450) is a very important metabolize enzyme, itresponsible for series endogenous and exogenous substances including thedrug metabolism. Research shows that factors affect the metabolism ofCYP450enzyme activity playing a crucial role on drug efficacy and sideeffects, could cause drug therapy effect of reducing or serious adversereactions. The food we eat in daily life could also inhibit or induce theactivity of CYP450enzyme. Therefore, people pay more and more attentionto the food-drug interaction.Celery possesses lots of pharmacological effects, it can flat liverstep-down, diuresis detumescence et al. Celry has been developed into avariety of health care products and drug listed current. Previous study reportfrom the pharmacodynamics showed that celery extract could inhibit theactivity of CYP450in mice, which indicated that celery could causefood-drug interactions, and even result the risk for drug safe use. CYP2A6isone important member of the family of CYP2A in CYP450, it responsiblefor the metabolism of some drugs, such as the valproic acid sodium,caffeine and nicotine, and closely related to smoking addiction. CYP2A5inmice and human’s CYP2A6have a high degree of homology, and have the similar function with CYP2A6. Thus, CYP2A5in mice is often used asearly study of the model of CYP2A6. Although previous researchers hadfound celery extract could affect some drug metabolism enzymes, butwhether it would impact on CYP2A6in the human body and its influencemechanism was also still not clearly now.We filtrated celery petroleum ether extract as the experimental subjectin the study at first, and then studied the effect of celery extract on CYP2A6.This study begin with the mouse liver microsomes as the research object,determined the influence of celery petroleum ether extract on CYP2A5, thenstudied the effect of petroleum ether extract on liver microsomal CYP2A6.Results showed that the petroleum ether extract of celery could inhibit theactivity of CYP2A5/2A6enzyme, the inhibition of celery petroleum etherextract on CYP2A5belong to a reversible inhibition, the Kiwas277.5μg·L-1;but it is an irreversible inhibition for CYP2A6, KI=1.055mg·ml-1, Kinact=0.315min. Finally verified the inhibit effect in vivo in mice, compared theinvestigated in vitro of celery petroleum ether extract on CYP2A5/2A6, andwe also analyzed the interaction mechanism. In vivo tests, we found that theactivity of CYP2A5was induced about16.7%in drug group than thecontrol group, which further proved that the celery extract could inhibit theactivity of CYP2A5, which suggested celery extract could also affectCYP2A6.In this study, we investigated the effect of celery petroleum ether extract on CYP2A5/2A6in vitro and in vivo in mice and in human livermicrosomes. From the results we confirmed:1) celery petroleum etherextract could inhibit the activity of CYP2A5in mice and CYP2A6inhuman， and for the species difference the inhibition mechanism weredifferent;2) Not only for the furocoumarin in celery, but also some otheringredients play the common role in the inhibition;3) Celery petroleumether extract could inhibit the activity of CYP2A5/2A6in vivo, so weshould avoid this kind of food and drug interaction when use the drug whichmetabolized by CYP2A6.