Study On The Effect Of Chinese Medicine Compound UCG On Cytochrome P450 Enzyme Based On Cocktail Probe Method

Traditional Chinese medicine(TCM),as a treasure of China,has a unique effect in the treatment of disease.Compared with Western medicine,TCM is usually considered natural,safe and non-toxic.Therefore it takes the attention of majority of the people.But in recent years,safety problems of TCM were reported usually.The National Drug Adverse Drug Reaction Center received 17.3% adverse reaction reports of TCM in 2014.The safety of TCM has aroused people's attention.Cytochrome P450 enzyme(CYP450)has a rich content in the liver and plays an important role in the metabolism of drugs.The activity of CYP450 increased or decreased may easily lead to drug-drug interactions and change the drug in vivo bioavailability,which would affect the curative effect of drugs and even lead to toxic effects.UCG is an effective drug for the treatment of chronic renal failure,which was in combination with losartan,simvastatin and other Western medicine in clinical treatment.In this study,five CYP isoforms,CYP1A2,2C9,2D6,2E1 and 3A4 were selected as the research object.A method bases on HPLC-TOF/MS was established to detect five specific metabolites of CYP isoforms simultaneously.The effect of UCG and its main medicinal materials(Glycyrrhizae,Rhubarb,Polygonum multiflorum,Sophora flavescens)and components(glycyrrhetinic acid,rhein,stilbene glucoside and matrine)on CYP450 enzyme activity was studied by cocktail probe method.1.To establish an adenine-induced rat model of chronic renal failure.The cytochrome P450 activity of liver microsomes was determined by cocktail probe method.The results showed that compared with normal group,the activity of CYP1A2 was significantly increased and the activity of CYP2C9,2D6,2E1 and 3A4 was significantly decreased in the model group.The clinical drug used in patients with chronic renal failure should take full account of drug-drug interaction caused by the inhibition of enzyme activity.2.To investigate the changes of CYP450 activity induced by UCG in the treatment of chronic renal failure.The activity of CYP450 was determined by cocktail probe method.The results showed that the activities of CYP1A2,2C9,2D6 and 3A4 in the UCG group were improved compared with the model group.UCG intervention in chronic renal failure rats for 12 weeks can down-regulate the activity of CYP1A2,2C9,CYP2D6 and up-regulate the activity of CYP3A4,which may affect the bioavailability of drugs metabolized by these enzymes,such as triamterene,losartan,cenafacaine,calcitriol and simvastatin.When UCG and these Western medicine are in combination for the treatment of kidney disease,it should be timely adjustment of dosage,to avoid adverse reactions.3.The cocktail probe method was used to determine the effect of compatibility of Rhubarb,Polygonum multiflorum,Sophora flavescens and Glycyrrhizae on cytochrome P450 activity.The effect of Rhubarb,Polygonum multiflorum and Sophora flavescens that was reported to have hepatotoxicity on cytochrome P450 activity in chronic renal failure system is less than that in normal system,which can reduce the drug interaction caused by the change of enzyme activity and reflect the thought of "you fu wu yun" to some extent.4.The effect of glycyrrhetinic acid,rhein,stilbene glycoside and matrine on cytochrome P450 activity was determined by the cocktail probe method.The result shows that the regulation trend of rhein,stilbene glycoside and matrine on CYP450 enzyme is basically consistent with Rhubarb,Polygonum multiflorum and Sophora flavescens,which suggests that rhein,stilbene glycosides,matrine may be the important components that affect the activity of Rhubarb,Polygonum multiflorum,Sophora flavescens on CYP450.