He Chi-Yu, Fu Jie, Shou Jia-Wen, Zhao Zhen-Xiong, Ren Long, Wang Yan, Jiang Jian-Dong
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing 100050, China.
Molecules. 2017 Jun 4;22(6):932. doi: 10.3390/molecules22060932.
Gut microbiota is populated with an immense number of microorganisms, which can be regulated by dietary components and drugs to markedly affect the nutritional and health status of the host. Eight medicinal isoquinoline alkaloids from natural plants were cultured anaerobically with rat gut microbiota and an LC/MS-IT-TOF technique was used to identify the resulting metabolites. Palmatine, tetrahydropalmatine, dauricine, and tetrandrine containing nitro-hexatomic isoquinoline rings could be easily transformed by the intestinal flora in vitro and a total of nine demethylated metabolites were detected. However, sinomenine, homoharringtonine, harringtonine, and galanthamine, which all contained benzazepine, could not undergo demethylation. Computer-assisted docking was used to analyze the binding between these compounds and sterol 14α-demethylase. The computational results demonstrated that hydrophobic interactions were the main driving force for binding, but the steric hindrance produced by the benzazepine structure resulted in a weak interaction between the hit compounds and the enzyme. This work illustrated that gut microbiota were important in the metabolism of isoquinoline alkaloids.
肠道微生物群中存在着大量的微生物，其可受饮食成分和药物的调节，从而显著影响宿主的营养和健康状况。将来自天然植物的八种药用异喹啉生物碱与大鼠肠道微生物群进行厌氧培养，并采用液相色谱/质谱-离子阱-飞行时间技术鉴定产生的代谢产物。含有硝基六元异喹啉环的巴马汀、四氢巴马汀、蝙蝠葛碱和粉防己碱在体外可被肠道菌群轻易转化，共检测到九种去甲基代谢产物。然而，均含有苯并氮杂卓的青藤碱、高三尖杉酯碱、三尖杉酯碱和加兰他敏则不能发生去甲基化。采用计算机辅助对接分析这些化合物与甾醇14α-去甲基酶之间的结合情况。计算结果表明，疏水相互作用是结合的主要驱动力，但苯并氮杂卓结构产生的空间位阻导致命中化合物与该酶之间的相互作用较弱。这项工作表明肠道微生物群在异喹啉生物碱的代谢中起着重要作用。
