药学学报, 2014, 49(12): 1705-1710
引用本文:
毕云枫, 郑重, 皮子凤, 刘志强, 宋凤瑞. 川乌与白芍配伍对CYP450酶活性影响及其代谢指纹的研究[J]. 药学学报, 2014, 49(12): 1705-1710.
BI Yun-feng, ZHENG Zhong, PI Zi-feng, LIU Zhi-qiang, SONG Feng-rui. The metabolic fingerprint of the compatibility of Radix Aconite and Radix Paeoniae Alba and its effect on CYP450 enzymes[J]. Acta Pharmaceutica Sinica, 2014, 49(12): 1705-1710.

川乌与白芍配伍对CYP450酶活性影响及其代谢指纹的研究
毕云枫1,2, 郑重1, 皮子凤1, 刘志强1, 宋凤瑞1
1. 中国科学院长春应用化学研究所, 国家质谱中心 (长春), 吉林省中药化学和质谱重点实验室, 吉林 长春 130022;
2. 吉林农业大学食品科学与工程学院, 吉林 长春 130118
摘要:
利用UPLC-MS/MS的多反应监控 (MRM) 技术, 结合多探针底物方法, 评价川乌-白芍配伍对肝脏主要药物代谢酶CYP 1A2、CYP 2C、CYP 2E1、CYP 2D、CYP 3A的活性影响.结果表明: 与川乌单煎液相比, 白芍与川乌不同配比溶液均能降低川乌对CYP3A、CYP2D、CYP2C及CYP1A2的抑制作用, 而对CYP2E1基本无影响.制川乌组分-白芍配伍溶液的CYP代谢指纹图谱分析结果表明, 与川乌单煎液相比, 共煎液经CYP代谢后双酯型生物碱的丰度明显降低, 而单酯型生物碱的丰度明显增加.表明白芍与川乌共用, 能使川乌中的双酯型毒性生物碱加快降解, 生成抗炎活性较好的单酯型生物碱, 起到减毒增效的作用.
关键词:    川乌      白芍      CYP450      代谢指纹图谱      减毒      增效     
The metabolic fingerprint of the compatibility of Radix Aconite and Radix Paeoniae Alba and its effect on CYP450 enzymes
BI Yun-feng1,2, ZHENG Zhong1, PI Zi-feng1, LIU Zhi-qiang1, SONG Feng-rui1
1. National Center of Mass Spectrometry in Changchun and Key Laboratory of Chinese Medicinal Chemistry and Mass Spectrometry in Jilin Province, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun 130022, China;
2. College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China
Abstract:
Using a UPLC-MS/MS (MRM) and cocktail probe substrates method, the metabolic fingerprint of the compatibility of Radix Aconite (RA) and Radix Paeoniae Alba (RPA) and its effect on CYP450 enzymes were investigated. These main CYP isoforms include CYP 1A2, CYP 2C, CYP 2E1, CYP 2D and CYP 3A. Compared with the inhibition effect of RA decoctions on CYP450 isoforms, their co-decoctions of RA and RPA with different proportions can decrease RA' inhibition on CYP3A, CYP2D, CYP2C and CYP1A2, but can not reduce RA' effect on CYP2E1. The metabolic fingerprints of RA decoction and co-decoctions with different proportions of RPA in CYP450 of rat liver were analyzed by UPLC-MS. Compared with the metabolic fingerprints of RA decoction, the intensity of diester-diterpenoid aconitum alkaloids decreased significantly, while the intensity of monoester-diterpenoid alkaloids significantly increased in the metabolic fingerprints of co-decoctions of RA and RPA. The results suggest that RA coadministration with RPA increased the degradation of toxic alkaloid and show the effect of toxicity reducing and efficacy enhancing.
Key words:    Radix Aconite    Radix Paeoniae    cytochrome P450    metabolic fingerprint    toxicity reducing    efficacy enhancing    
收稿日期: 2014-06-16
基金项目: 国家自然科学基金资助项目(81073040,81274046);国家重点基础研究发展计划(973计划)资助项目(2011CB505300,2011CB505305).
通讯作者: 宋凤瑞
Email: songfr@ciac.ac.cn
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