Exploring in vitro, in vivo metabolism of mogroside V and distribution of its metabolites in rats by HPLC-ESI-IT-TOF-MS(n).
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.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, China.
Feng
F
Xu
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. Electronic address: ldp@gxib.cn.
Dian-Peng
DP
Li
Department of Pharmacy, Guangxi Hezhou Municipal People's Hospital, Hezhou 542899, China.
Zhen-Cong
ZC
Huang
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.
Feng-Lai
FL
Lu
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.
Lei
L
Wang
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.
Yong-Lin
YL
Huang
Beijing University of Chinese Medicine, Beijing 100102, China.
Ru-Feng
RF
Wang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, China.
Guang-Xue
GX
Liu
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, China.
Ming-Ying
MY
Shang
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, No. 38 Xueyuan Road, Beijing 100191, China. Electronic address: sqcai@hsc.pku.edu.cn.
Shao-Qing
SQ
Cai
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D006031:Glycosylation; D006801:Humans; D006900:Hydroxylation; D007422:Intestines / Q000382:microbiology; D008297:Male; D008745:Methylation; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization; D013549:Sweetening Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014315:Triterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics*
D004365:Drugs, Chinese Herbal; D013549:Sweetening Agents; D014315:Triterpenes; C041740:mogroside V
LC-ESI-IT-TOF-MS(n); Metabolite distribution; Mogrol; Mogroside V; Saponin; Siraitia grosvenorii