Li Zhao-liang, Dong Xian-zhe, Wang Dong-xiao, Dong Rui-hua, Guo Ting-ting, Sun Yan, Liu Ping
Zhongguo Zhong Yao Za Zhi. 2014 Nov;39(22):4459-63.
Five compounds (tenuifoliside C, tenuifoliside D, telephiose A, telephiose C and polygalaxanthone III) from polygala tenuifolia wild were incubated together with CYP probe substrate in human liver microsomes to investigate the inhibitory effect towards CYP450 enzyme. Phenacetin (CYP1A2), coumarin (CYP2A6), paclitaxel (CYP2C8), diclofenac (CYP2C9), S-mepheriytoin (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1), midazolam (CYP3A) were selected as the isoforfn specific substrate. And the formation of paracetamol, 7-hydroxycoumarin, 6alpha-hydroxy paclitaxel, 4'-hydroxydiclofenac, dextrorphan, 6-hydroxychlorzoxazone, 1'-hydroxymidazolam, 4'-hydroxymephenytoin were detected respectively to measure the effect towards CYP450 by high-pressure liquid chromatography (HPLC). The result shows that five compounds from polygala tenuifolia willd significantly inhibit chlorzoxazone 6-hydroxylation catalyzed by CYP2E1, while showed no effect towards CYP1A2, CYP2A6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A. And IC50 value was 38.73, 54.14, 61.77, 62.22, 50.56 micromol x L(-1), respectively.
将远志中的5种化合物（细叶远志苷C、细叶远志苷D、长梗远志苷A、长梗远志苷C和广寄生苷III）与人肝微粒体中的CYP探针底物共同孵育，以研究其对CYP450酶的抑制作用。选择非那西丁（CYP1A2）、香豆素（CYP2A6）、紫杉醇（CYP2C8）、双氯芬酸（CYP2C9）、S-美芬妥因（CYP2C19）、右美沙芬（CYP2D6）、氯唑沙宗（CYP2E1）、咪达唑仑（CYP3A）作为同工酶特异性底物。分别检测对乙酰氨基酚、7-羟基香豆素、6α-羟基紫杉醇、4'-羟基双氯芬酸、右啡烷、6-羟基氯唑沙宗、1'-羟基咪达唑仑、4'-羟基美芬妥因的生成量，通过高效液相色谱（HPLC）测定对CYP450的作用。结果表明，远志中的5种化合物对CYP2E1催化的氯唑沙宗6-羟基化有显著抑制作用，而对CYP1A2、CYP2A6、CYP2C8、CYP2C9、CYP2C19、CYP2D6、CYP3A无作用。IC50值分别为38.73、54.14、61.77、62.22、50.56 μmol·L-1。
