| 乌头类生物碱组分在CYP450中的代谢指纹图谱及对CYP450活性的影响 |
| |
| 引用本文： | 毕云枫,刘舒,李雪,刘志强,宋凤瑞.乌头类生物碱组分在CYP450中的代谢指纹图谱及对CYP450活性的影响[J].高等学校化学学报,2013,34(9):2084-2089. |
| |
| 作者姓名： | 毕云枫 刘舒 李雪 刘志强 宋凤瑞 |
| |
| 作者单位： | 1. 中国科学院长春应用化学研究所, 化学生物学实验室&长春质谱中心, 长春 130022;
2. 吉林农业大学食品科学与工程学院, 长春 130118 |
| |
| 基金项目： | 国家自然科学基金(批准号:81073040,81274046);国家“九七三”计划项目(批准号:2011CB505300,2011CB505305)资助 |
| |
| 摘 要： | 利用超高效液相色谱-串联质谱(UPLC-MS/MS)的多反应监测(MRM)技术, 结合多探针底物方法, 对单酯型及双酯型乌头类生物碱组分对细胞色素P450(CYP450)亚型的活性影响进行了研究; 同时利用超高效液相色谱-四极杆-飞行时间串联质谱(UPLC-Q-TOF-MS/MS)对单酯型和双酯型乌头类生物碱组分在CYP450中的代谢指纹图谱进行了研究. 活性影响研究结果表明, 单酯型生物碱组分对CYP2C及2D的抑制能力较强, 其IC50值分别为7.44和6.74 μmol/L; 双酯型生物碱组分对CYP1A2, 3A, 2C和2D均有较弱的抑制作用, 其IC50值分别为39.48, 70.44, 17.36和86.04 μmol/L. 代谢指纹图谱显示, 双酯型生物碱组分在大鼠肝微粒体中有6个特异性产物可以作为该反应的特征峰.
|
| 关 键 词： | 乌头类生物碱 细胞色素P450 代谢指纹图谱 超高效液相色谱-串联质谱 多探针底物 |
| 收稿时间： | 2013-05-27 |
Metabolic Fingerprint and Effects of Aconite Alkaloid Components on the Activities of CYP450 Isozymes in Rat Liver Microsomes |
| |
| BI Yun-Feng;LIU Shu;LI Xue;LIU Zhi-Qiang;SONG Feng-Rui.Metabolic Fingerprint and Effects of Aconite Alkaloid Components on the Activities of CYP450 Isozymes in Rat Liver Microsomes[J].Chemical Research In Chinese Universities,2013,34(9):2084-2089. |
| |
| Authors: | BI Yun-Feng;LIU Shu;LI Xue;LIU Zhi-Qiang;SONG Feng-Rui |
| |
| Institution: | 1. Chemcial Biology Laboratory & Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China;
2. College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China |
| |
| Abstract: | The effects of the components of monoester and diester diterpenoid alkaloids(MDAs, DDAs) on the activities of hepatic microsomal CYP450 isozymes(CYP1A2, CYP2C, CYP2E1, CYP2D, CYP3A) were studied by ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) combined with cocktail probe substrate' s method. The metabolic fingerprints of MDAs and DDAs' components were studied in rat liver microsomes using UPLC-Q-TOF/MS/MS. The results showed that the components of MDAs had strong inhibitory effects on the activities of CYP2C and 2D, the IC50 value was 7.44 and 6.74 μmol/L, respectively. The components of DDAs had weaker inhibitory effects on the activities of CYP1A2, 3A, 2C and 2D, the IC50 value was 39.48, 70.44, 17.36 and 86.04 μmol/L, respectively. Six metabolites of DDAs in rat liver microsomes were identified using UPLC-Q-TOF-MS/MS. They can be used as marked peaks for metabolic fingerprint of aconite alkaloids components. |
| |
| Keywords: | Aconite alkaloid Cytochrome P450 Metabolic fingerprint Ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) Cocktail probe substrate |
| 本文献已被 CNKI 等数据库收录！ |
| 点击此处可从《高等学校化学学报》浏览原始摘要信息 |
| 点击此处可从《高等学校化学学报》下载免费的PDF全文 |
|
