黄皮酰胺类化合物及五味子素衍化物对小鼠肝细胞色素P-450的诱导作用

 目的 观察3种黄皮酰胺类化合物新黄皮酰胺(neoclausenamide,Neo-cl)、辛黄皮酰胺(zeta-clausenamide,Zeta-cl)、原黄皮酰胺(secoclausenamide,Seco-cl)及五味子素衍化物(SE-31)对小鼠肝药酶是否有诱导作用。方法 小鼠每日ig所试化合物1次，共3 d，测定肝微粒体细胞色素P-450的含量，以及依赖细胞色素P-450的相关酶活性，并观察所试化合物提前1 h和24 h给药对注射戊巴比妥钠小鼠睡眠时间的影响。结果 Neo -cl,Zeta-cl和Seco-cl及SE-31给药3次对小鼠肝药酶都有显著的诱导作用；这几种化合物提前1 h给药可明显延长戊巴比妥钠所致小鼠的睡眠时间，提前24 h给药则可明显缩短睡眠时间。Seco-cl和SE-31在体外与肝微粒体共温孵可明显抑制氨基比林脱甲基酶活性。结论 Neo-cl，Zeta-cl和Seco-cl及SE-31对小鼠肝药酶都有显著的诱导作用，且几种化合物对肝药酶均表现出先抑制后诱导的双相作用。

Inductive effects of clausenamide compounds and schisandrin derivative on liver cytochrome P-450 in mice

OBJECTIVE To investigate the hepatoprotective effects of four compounds neoclausenamide,zeta-clausenamide,secoclausenamide and SE-31,a derivative of schisandrin) on liver cytochrome P-450 in mice. METHODS Those mice were orally given the test compound once daily for 3 days.The liver microsomes were prepared and its cytochrome P-450 content and P-450-dependent enzymes activities were determined.In another experiment,the mice were given the compounds 1 hour or 24 hour before ip injection of 50 mg·kg^-1sodium pentobarbital,their sleeping time was recorded.Secoclausenamide and SE-31 were incubated with liver microsomes in vitro,then the activity of aminopyrine-N-demethylase activity APDM) was determined. RESULTS Neoclausenamide,zeta-clausenamide,secoclausenamide and SE-31 significantly increased the content of cytochrome P-450 and its related enzymes activities.When all these compounds were administered 1 hour before injection of sodium pentobarbital,the sleeping time was prolonged markedly.The sleeping time was shortened significantly when the compounds were given 24 hour before injection of pentobarbital.Secoclausenamide and SE-31 inhibited the microsomal APDM activity in vitro. CONCLUSION All of neoclausenamide,zeta-clausenamide secoclausenamide and SE-31 showed inducton effects on liver cytochrome P-450 through biphase:first inhibition and followed by induction.