Seervi Madhav, Lotankar Shweta, Barbar Shrikant, Sathaye Sadhana
Drug Metab Pers Ther. 2016 Jun 1;31(2):115-22. doi: 10.1515/dmpt-2015-0043.
Lupeol and betulin are triterpenoids that are majorly found in dietary substances. The aim of present study was to investigate the inhibition and induction potential of lupeol and betulin on cytochrome P450 (CYP)1A2, CYP2C11, CYP2D6 and CYP3A2 activities in rat liver microsomes.
The inhibition and induction studies were conducted using ethoxy resorufin-O-deethylase (CYP1A2), tolbutamide hydroxylase (CYP2C9), and midazolam hydroxylase (CYP3A4) activity assays. In vitro inhibition study was evaluated by incubating lupeol and betulin (1, 3, 10, 30 and 100 μM) with rat liver microsomes, and the metabolite formation was analyzed by high-performance liquid chromatography. The induction study was conducted by administering lupeol (20 mg/kg) and betulin (50 mg/kg) intraperitoneally for 14 days to rats followed by liver isolation and microsome preparation.
The IC50 values in inhibition studies were found to be 59.42 μM (CYP1A2), >100 μM (CYP2C11, CYP2D6, CYP3A2) for lupeol, 52.24 μM (CYP1A2), and >100 μM (CYP2C9, CYP2D6, CYP3A2) for betulin. There was no significant modification observed in the CYP450 isoforms, indicating neither inhibition nor induction potential of lupeol and betulin.
Lupeol and betulin have very low propensity to interact with CYP enzyme, suggesting no CYP inhibitory and inducing potential in rat liver microsomes.
羽扇豆醇和桦木醇是主要存在于饮食中的三萜类化合物。本研究旨在探讨羽扇豆醇和桦木醇对大鼠肝微粒体中细胞色素P450（CYP）1A2、CYP2C11、CYP2D6和CYP3A2活性的抑制和诱导潜力。
使用乙氧基试卤灵-O-脱乙基酶（CYP1A2）、甲苯磺丁脲羟化酶（CYP2C9）和咪达唑仑羟化酶（CYP3A4）活性测定法进行抑制和诱导研究。通过将羽扇豆醇和桦木醇（1、3、10、30和100μM）与大鼠肝微粒体孵育来评估体外抑制研究，并通过高效液相色谱法分析代谢物形成。诱导研究是通过向大鼠腹腔注射羽扇豆醇（20mg/kg）和桦木醇（50mg/kg）14天，然后分离肝脏并制备微粒体来进行的。
在抑制研究中，羽扇豆醇对CYP1A2的IC50值为59.42μM，对CYP2C11、CYP2D6、CYP3A2大于100μM；桦木醇对CYP1A2的IC50值为52.24μM，对CYP2C9、CYP2D6、CYP3A2大于100μM。在CYP450同工型中未观察到显著变化，表明羽扇豆醇和桦木醇既无抑制潜力也无诱导潜力。
羽扇豆醇和桦木醇与CYP酶相互作用的倾向非常低，表明在大鼠肝微粒体中无CYP抑制和诱导潜力。
