Metabolic characteristics of neferine in the cytochrome P450 of rat liver microsomes / 中国药理学通报

ABSTRACT

Aim The metabolic character of neferine(Nef) in rat liver microsomes was studied in vitro to identify which isoforms of cytochrome P450 were responsible for Nef metabolism in rats.Methods ① Wistar rats were untreated or treated with various inducers including dexamethasone(DEX,50 mg?kg~(-1),ig?4 d),phenobarbital(PB,75 mg?kg~(-1),ip?3 d) and ?-naphthoflavone(?-NF,80 mg?kg~(-1),ip?3 d).Liver microsomes were obtained from these rats and incubated with Nef in the presence of reduced form of nicotinamide adenine dinucleotide phosphate.A HPLC-UV method was developed to determine Nef and its metabolites.② The enzyme kinetics of the metabolism of Nef was investigated in rat liver microsomes.③ Troleandomycin,a CYP3A selective inhibitor,was used to study its inhibitory effect on the metabolism of Nef in vitro.Results ① The metabolism of Nef in rat liver microsomes showed the characteristic of enzymekinetics.② The correlation between peak area of a metabolite and original concentration of Nef in rat liver microsomes solution was significant(r=0.993).③ The disappearing rate of Nef in the incubation solutions of the rats liver microsomes,which treated with DEX or PB,were markedly quicker than that of control group(P0.05).The average disappearing rates of Nef in rat liver microsomes after incubation with different inducers were as follows DEX,80.6%?9.5%;PB,61.5%?6.7%;?-NF,20.7%?1.5%;Control,19.9%?1.6%.④ Troleandomycin could significantly inhibit the metabolism of Nef in rat liver microsomes.Conclusion Our results suggest that both CYP3A and CYP2B are involved in Nef metabolism in rats liver microsomes,and CYP3A probably play a major role.