Gender differences in cytochrome P450 enzyme and UDP-glucuronosyltransferase mediated metabolic stabilities of bakuchiol in rat and human liver microsomes / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE: To investigate the metabolic characteristics of bakuchiol mediated by cytochrome P450 enzyme (CYP) and UDP-glucuronosyltransferase (UGT) in rat liver microsomes (RLMs) or human liver microsomes (HLMs), and to compare the metabolic gender differences. METHODS: Bakuchiol was incubated at 37? with male and female RLMs or HLMs in the presence of nicotinamide adenine dinucleotide phosphate (NADPH) or uridine 5′-diphosphoglucuronic acid (UDPGA). The residual concentrations of bakuchiol were measured in each incubation system using high performance liquid chromatography (HPLC). The metabolic stability and metabolic gender differences of bakuchiol were evaluated by the remaining percentage of bakuchiol after incubation.RESULTS: When bakuchiol was metabolized by CYP in RLMs, the intrinsic clearance (Clint) value in male RLMs ?(326.6±15.4) mL·min-1·kg-1?was significantly higher than that of female RLMs ?(77.2±4.8) mL·min-1·kg-1? (P<0.01). When bakuchiol was metabolized by UGT in RLMs, female RLMs had a significantly higher Clint value ?(419.1±24.1) mL·min-1·kg-1? than male RLMs ?(164.5±8.4) mL·min-1·kg-1? (P<0.01). When bakuchiol was metabolized by both CYP and UGT in RLMs, male RLMs had a significantly higher Clint value ?(1063.1±27.2) mL·min-1·kg-1? than female RLMs ?(781.2±16.5) mL·min-1·kg-1?(P<0.01). When bakuchiol was metabolized by CYP in HLMs, male HLMs had a significantly higher Clint value ?(24.8±2.1) mL·min-1·kg-1? than female HLMs ?(17.6±1.0) mL·min-1·kg-1? (P<0.01). There were no significant gender differences in the metabolism of bakuchiol when it was metabolized by UGT in HLMs. The Clint values were 176.4±26.5 and (165.9±8.6) mL·min-1·kg-1, respectively. The metabolic parameters of bakuchiol mediated by CYP and UGT in HLMs had no significant gender differences. The Clint values were 262.5±20.9 and (236.2±10.5) mL·min-1·kg-1, respectively. CONCLUSION Bakuchiol can be metabolized by CYP and UGT in RLMs or HLMs, and the metabolic parameters exhibit species differences and gender differences.