title: Ardipusilloside-I Metabolites from Human Intestinal Bacteria and Their Antitumor Activity.
abstract: Ardipusilloside-I (ADS-I) is a triterpenoid saponin extracted from Ardisia pusilla DC, and has been demonstrated to have potent antitumor activity. However, ADS-I metabolism in humans has not been investigated. In this study, we studied the biotransformation of ADS-I in human intestinal bacteria, and examined the in vitro antitumor activity of the major metabolites. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to detect ADS-I biotransformation products, and their chemical structures were identified by high performance liquid chromatography-nuclear magnetic resonance (HPLC-NMR). The antitumor activity of the major metabolites was determined by the MTT assay. Here, we show that main reaction seen in the metabolism of ADS-I in human intestinal bacteria was deglycosylation, which produced a total of four metabolites. The structures of the two major metabolites M1 and M2 were confirmed by using NMR. MTT assay showed that ADS-I metabolites M1 and M2 have the same levels of inhibitory activities as ADS-I in cultured SMMC-7721 cells and MCF-7 cells. In conclusion, this study demonstrates deglycosylation as a primary pathway of ADS-I metabolism in human intestinal bacteria, and suggests that the pharmacological activity of ADS-I may be mediated, at least in part, by its metabolites.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. weiyu_cao@163.com.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. wangyanan@imm.ac.cn.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. peng_yuanwang@163.com.
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. wanlei_fmmu@163.com.
authors.forename: Wan
authors.initials: W
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. binfengfmmu@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Pharmacy, School of Stomatology, The Fourth Military Medical University, Xi'an 710032, China. kqyyyjk@fmmu.edu.cn.
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D000069196:Gastrointestinal Microbiome; D006801:Humans; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; D010936:Plant Extracts; D012503:Saponins; C087799:ardipusilloside I; D009828:Oleanolic Acid
keywords: HPLC–NMR; UHPLC–MS; antitumor activity; ardipusilloside-I; human intestinal bacteria; metabolism