Study On The Effect Of Gelsemium And Macleaya Cordata To Drug Metabolizing Enzymes

Chinese herbal medicine has been widely used in clinical treatment of human and veterinary medicine,owing to their excellent traits of being environmentally friendly and safe.Lots of studies showed that Chinese herbal medicine had effect on the activity of cytochrome P450 and other drug-metabolizing enzymes,which causing herb-drug interactions and increasing some risk of adverse drug events.Thus,it becomes necessary to study the herb-drug interactions.More recently,food supplements derived from Gelsemium Elegans Benth.and Macleaya cordata have been fed to farm animals so that it is very important to investigate the influence of Gelsemium Elegans Benth.and Macleaya cordata on drug metabolizing enzymes.Objective: This study was to investigate effects of the Gelsemium Elegans Benth.and Macleaya cordata alkaloids(allocryptopine,protopine,sanguinarine and chelerythrine)on CYP450(CYP)and NAD(P)H: Quinone Oxidoreductase(NQO1)activities.Methods: The activities of CYP450(CYP)in the microsomes were determined by chemical colorimetry in vivo and vitro.The inhibitor method was used to evaluated the activities of(NAD(P)H: quinine oxidoreductase type 1(NQO1)in liver cytosolic in rat and swine.Results: The experimental results in vitro showed that the activities of AND could induce by protopine and allocryptopine in swine liver microsomes,while the activities of ERND were inhibited by the former.In addition,protopine at 10?g/mL significantly induced AND activity increased by 61.46% in rats,but had no significant effect on ERND.The experimental results in vivo indicated that the activities of AND and ERND in liver microsomes of female rat can be improved by Plume Poppy Extract and Plume Poppy Total Protopine Alkaloid,in which the improving effect of the former was more significant than the latter.However,Plume Poppy Extract treated male rats showed an increase in AND and ERND activity with no significant difference;While reducing effects was founded in Plume Poppy Total Protopine Alkaloid in treated male rats,especially in group of 48 h.More interestingly,the NQO1 activity was induced by them only in female rats,but much lower NQO1 activities were observed in male rats.Moreover,the alcohol and acid water extract of Gelsemium total alkaloids treated can influenced the activity at all concentration(25,50,100?g /mL)in swine liver microsomes,compared with control group,and powerfully inhibit NQO1 activity(70%).Furthermore,we established that the protopine and sanguinarine can inhibit NQO1 activity in swine and rats.The inhibition rate of protopine was about 50% at 20?M in swine and rat,while the inhibition rate of sanguinarine was about 16% and 30% at 40?M in swine and rat,respectively.And the inhibition of them were reversible and uncompetitive.The Ki calculated for protopine and sanguinarine as an uncompetitive inhibitor of swine NQO1 was 4.12 ?mol/L and 132.82 ?mol/L,respectively,and the Ki of rat NQO1 was 15.96?mol/L and 42.71 ?mol/L.On the other hand,we found that allocryptopine and chelerythrine had no inhibitory effect on NQO1.Conclusion: The extract of Gelsemium showed induction effect on swine CYP,while had inhibitory effect on NQO1;The activities of CYP in liver microsomes of female rat could be improved by Plume Poppy Extract and Plume Poppy Total Protopine Alkaloid.Plume Poppy Extract could induce the CYP activity in male rat,on the contrary,which reduced by Plume Poppy Total Protopine Alkaloid.Furthermore,the influence of Macleaya cordata and Gelsemium Elegans Benth on NQO1 activity in male and female rats were also opposite.The results suggested that intake of Gelsemine and Macleaya cordata may lead to herbal-drug interactions and provides scientific basis for rational drug use.