Xu Feng, Li Dian-Peng, Huang Zhen-Cong, Lu Feng-Lai, Wang Lei, Huang Yong-Lin, Wang Ru-Feng, Liu Guang-Xue, Shang Ming-Ying, Cai Shao-Qing
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, China.
Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Guangxi Zhuang Autonomous Region and Chinese Academy of Sciences, No. 85, Yanshan Road, Yanshan District, Guilin 541006, China.
J Pharm Biomed Anal. 2015 Nov 10;115:418-30. doi: 10.1016/j.jpba.2015.07.024. Epub 2015 Jul 26.
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 9000g 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-MS(n)). 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.
罗汉果甜苷V是一种葫芦烷型皂苷，不仅是传统中药罗汉果的主要生物活性成分，也是一种广泛使用的甜味剂。为阐明其生物转化过程并确定其体内有效形式，我们研究了其在人肠道细菌培养系统、大鼠肝脏9000g上清液（S9）培养系统以及大鼠体内的代谢情况。同时，首次报道了罗汉果甜苷V及其代谢产物的分布情况。借助高效液相色谱串联电喷雾离子阱（IT）飞行时间多级质谱（HPLC-ESI-IT-TOF-MS(n)），鉴定出77种新代谢产物，其中包括由单羟基化至四羟基化/脱氢形成的52种氧化产物。具体而言，在人肠道细菌培养系统中鉴定出14种代谢产物，在肝脏S9培养系统中鉴定出4种，在粪便中鉴定出58种，在尿液中鉴定出29种，在血浆中鉴定出14种，在心脏中鉴定出34种，在肝脏中鉴定出33种，在脾脏中鉴定出39种，在肺中鉴定出39种，在肾脏中鉴定出42种，在胃中鉴定出45种，在小肠中鉴定出51种。提出了罗汉果甜苷V的代谢途径，鉴定出的代谢反应包括去糖基化、羟基化、脱氢、异构化、糖基化和甲基化。罗汉果甜苷V及其代谢产物在受试大鼠的器官中分布不均。鉴定出罗汉果甜苷V的7种生物活性代谢产物，其中罗汉果甜苷IIE在心脏、肝脏、脾脏和肺中含量丰富，表明它可能对罗汉果甜苷V的生物活性有贡献。罗汉果甜苷V主要经尿液排泄，而其代谢产物主要经粪便排泄。据我们所知，这是首次报道一种植物成分在体内可生物转化为65种以上代谢产物。这些发现将增进对罗汉果甜苷V及其同类分子的体内代谢、分布和有效形式的理解。
