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Abstract：
Kakkalide and irisolidone, the main isoflavones of Flos Puerariae, exhibit a wide spectrum of bioactivities. Intestinal bacteria biotransformation plays an important role in the metabolic pathways of flavones, and is directly related to the bioactivities of the prodrugs after oral administration. To the best of our knowledge, the metabolic pathways of kakkalide and irisolidone in vitro have not been comprehensively studied yet. This paper describes the strategy using ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF MS) for the rapid analysis of the metabolic profiles of kakkalide and irisolidone after incubated with human and rat intestinal bacteria. Bacteria incubated samples were prepared and analyzed after incubated under anaerobic conditions for 48 h. A total of 17 metabolites, including parent compounds, were detected in human and rat intestinal bacteria incubated samples. The results obtained indicate that hydrolysis, dehydroxylation, demethoxylation, demethylation, hydroxylation, decarbonylation, and reduction were the detected metabolic pathways of kakkalide and irisolidone in vitro. The conversion rate of irisolidone in human and rat bacteria was 8.57% and 6.51%, respectively. Biochanin A was the relatively main metabolite of irisolidone, and the content of biochanin A in human and rat bacteria was 3.68% and 4.25%, respectively. The conversion rate of kakkalide in human and rat bacteria was 99.92% and 98.58%, respectively. Irisolidone was the main metabolite of kakkalide, and the content of irisolidone in human and rat bacteria was 89.58% and 89.38%, respectively. This work not only provides the evidence of kakkalide and irisolidone metabolites in vivo, but also demonstrates a simple, fast, sensitive, and inexpensive method for identification of metabolites of other compounds transformed by intestinal bacteria.
摘要：
卡卡利德和依立索力酮,葛花的主要异黄酮，表现出广泛的生物活性。肠道细菌生物转化在黄酮的代谢途径中起着重要作用,并且与口服给药后前药的生物活性直接相关。据我们所知,kakkalide和irispolidone在体外的代谢途径尚未全面研究。本文介绍了使用超高效液相色谱/四极杆飞行时间质谱（UHPLC/Q-TOFMS）快速分析与人和大鼠肠道细菌孵育后的卡卡利特和依立索利酮的代谢谱的策略。在厌氧条件下培养48小时后，制备和分析细菌培养样品。总共17种代谢物，包括母体化合物，在人和大鼠肠道细菌孵育样品中检测到。获得的结果表明，水解，脱羟基,脱甲氧基化,去甲基化,羟基化,脱羰基,和还原是体外检测到的kakkalide和irispolidone的代谢途径。在人和大鼠细菌中，依立酮的转化率分别为8.57％和6.51％，分别。BiochaninA是相对主要的代谢产物,人和大鼠细菌中生物香精A的含量分别为3.68%和4.25%，分别。卡卡利德在人和大鼠细菌中的转化率分别为99.92％和98.58％，分别。卡卡列德的主要代谢产物为伊利沙利酮,人和大鼠细菌中依立酮的含量分别为89.58%和89.38%，分别。这项工作不仅提供了卡卡利德和依里索利酮代谢产物在体内的证据，但也展示了一个简单的，快,敏感,以及用于鉴定由肠道细菌转化的其他化合物的代谢物的廉价方法。
