Mogroside V, a cucurbitane-type saponin, is not only the major bioactive constituent of traditional Chinese medicine Siraitiae Fructus, but also a widely used sweetener. To clarify its biotransformation process and identify its effective forms in vivo, we studied its metabolism in a human intestinal bacteria incubation system, a rat hepatic 9000 g supernatant (S9) incubation system, and rats. Meanwhile, the distribution of mogroside V and its metabolites was also reported firstly. Seventy-seven new metabolites, including 52 oxidation products formed by mono- to tetra- hydroxylation/dehydrogenation, were identified with the aid of HPLC in tandem with ESI ion trap (IT) TOF multistage mass spectrometry (HPLC-ESI-IT-TOF-MSⁿ). Specifically, 14 metabolites were identified in human intestinal bacteria incubation system, 4 in hepatic S9 incubation system, 58 in faeces, 29 in urine, 14 in plasma, 34 in heart, 33 in liver, 39 in spleen, 39 in lungs, 42 in kidneys, 45 in stomach, and 51 in small intestine. The metabolic pathways of mogroside V were proposed and the identified metabolic reactions were deglycosylation, hydroxylation, dehydrogenation, isomerization, glucosylation, and methylation. Mogroside V and its metabolites were distributed unevenly in the organs of treated rats. Seven bioactive metabolites of mogroside V were identified, among which mogroside IIE was abundant in heart, liver, spleen and lung, suggesting that it may contribute to the bioactivities of mogroside V. Mogroside V was mainly excreted in urine, whereas its metabolites were mainly excreted in faeces. To our knowledge, this is the first report that a plant constituent can be biotransformed into more than 65 metabolites in vivo. These findings will improve understanding of the in vivo metabolism, distribution, and effective forms of mogroside V and congeneric molecules.

罗汉果苷V是一种葫芦素型皂苷，不仅是中药狼尾草的主要生物活性成分，还是一种广泛使用的甜味剂。为了阐明其生物转化过程并确定其体内有效形式，我们在人肠细菌培养系统，大鼠肝9000 g上清液（S9）培养系统和大鼠中研究了其代谢。同时，还首次报道了罗汉果苷V及其代谢物的分布。借助HPLC结合ESI离子阱（IT）TOF多级质谱（HPLC-ESI-IT-TOF- MS ^ñ）。具体而言，在人体肠道细菌培养系统中鉴定出14种代谢产物，在肝S9培养系统中鉴定出4种代谢产物，在粪便中发现58种，在尿液中发现29种，在血浆中发现14种，在心脏中发现34种，在肝脏中发现33种，在脾脏中发现39种，在肺中发现39种，在肺中发现42种。肾脏，胃中的45个和小肠中的51个。提出了罗汉果苷V的代谢途径，确定的代谢反应为去糖基化，羟基化，脱氢，异构化，糖基化和甲基化。罗汉果苷V及其代谢产物在受治疗大鼠的器官中分布不均。鉴定出罗汉果甙V的7种生物活性代谢产物，其中罗汉果甙IIE在心脏，肝脏，脾脏和肺中含量丰富，表明其可能有助于罗汉果甙V的生物活性。罗汉果甙V主要从尿中排泄，而其代谢物主要通过粪便排泄。据我们所知，这是第一份关于植物成分可以被生物转化为65种以上代谢产物的报告。体内。这些发现将增进对罗汉果苷V和同类分子的体内代谢，分布和有效形式的了解。