16-O-去甲基去氧乌头碱在肠内细菌中的生物转化研究

采用人肠内细菌和乌头碱体外温孵的方法,探讨乌头碱的代谢产物16-O-去甲基去氧乌头碱在人肠内的生物转化。利用离子阱电喷雾串联质谱(ESIMS/MSn)方法直接分析16-O-去甲基去氧乌头碱的代谢产物。乌头类生物碱在ESI正离子模式条件下形成质子化分子M H] 。16-O-去甲基去氧乌头碱可被人肠内细菌转化,通过脱乙酰基、脱苯甲酰基、脱甲基、脱羟基以及酯化反应产生新型的单酯型、双酯型和脂类生物碱等10余种代谢产物。双酯型生物碱具有较高的毒性,相对应的单酯型和脂类生物碱毒性较低。16-O-去甲基去氧乌头碱被肠内细菌转化为单酯型和脂类生物碱会使其毒性降低。

Studies on the Biotransformation of 16-O-demethyldeoxyaconitine of the Metabolite of Aconitine in Human Intestinal Bacteria

To study the biotransformation of 16-O-demethyldeoxyaconitine in human intestine,aconitine was incubated with human intestinal bacteria in vitro.The metabolites of 16-O-demethyldeoxy-aconitine were directly investigated using electrospray ionization tandem mass spectrometry(ESI-MSn).Aconitum alkaloids formed protonated molecule in the positive ion mode.16-O-demethyldeoxyaconitine can be transformed by human intestinal bacteria.It was converted into more than 10 kinds of new metabolites such as mono-ester alkaloids,diester alkaloids and lipo-alkaloids by deacetylation,debenzoyltion,dehydroxylation,demethylation and esterification.Diester alkaloids are very toxical.However,the toxicity of mono-ester alkaloids and lipo-alkaloids are less than that of diester alkaloids.When 16-O-demethyldeoxyaconitine was transfor med into mono-ester alkaloids and lipo-alkaloids by human intestinal bacteria,the toxicity degraded.