title: Metabolism and pharmacokinetics of major polyphenol components in rat plasma after oral administration of total flavonoid tablet from Anemarrhenae Rhizoma.
abstract: Total flavonoid tablet from Anemarrhenae Rhizoma (Zhimu tablet), which was made of total polyphenol components extracted from the dried rhizome of Anemarrhena asphodeloides Bge. (Zhimu in Chinese), is a novel traditional Chinese medicine prescribed for the treatment of diabetes. Mangiferin (MF) and neomangiferin (NMF) are the two main components detected and determined in Zhimu tablet, accounting for 8.9% of the total weight of each tablet. In the present study, high performance liquid chromatography (HPLC) coupled with time-of-flight (TOF) tandem mass spectrometry (MS) was applied to characterize the metabolites of MF and NMF in rat plasmas collected at different time points after oral administration of Zhimu tablet at a dose of 3.63g/kg (corresponding to 270mg/kg MF). Accurate mass measurement was used to determine the elemental composition of metabolites and thus to confirm the proposed structures of identified metabolites. Time points of appearance of some metabolites, such as isomers, were also taken into account during the structure confirmation. A total of 21 potential metabolites were found in rat plasma at different time points, and the metabolic pathways in vivo were involved in hydrolysis, methylation, glucuronide conjugation, glycoside conjugation, sulphation, dehydration and isomerisation. Furthermore, a selective and accurate LC-MS assay method was developed and validated for the quantification of MF in plasma. Semi-quantification of main conjugated metabolites was also performed in order to describe the dynamic metabolism profiles of polyphenol components in Zhimu tablet. MF concentration in plasma reached 1.36±0.47μgmL(-1) about 5.0h after oral administration of Zhimu tablet, which showed a 3.24- and 4.91-fold increase in plasma maximum concentration and area under the concentration-time curve (AUC) from 0 to 24h of MF compared with those for rats administered with free MF, respectively. The results indicated that the pharmacokinetic processes and bioavailability of MF in rats would be affected by other components in Zhimu tablet.
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Beijing Key Lab of Microanalytical Methods & Instrumentation, Department of Chemistry, Tsinghua University, Beijing 100084, China. Electronic address: yuanyuan_sy@mail.tsinghua.edu.cn.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Xie
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Beijing Key Lab of Microanalytical Methods & Instrumentation, Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Xiu-Ming
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Beijing Key Lab of Microanalytical Methods & Instrumentation, Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Si-Huan
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Beijing Key Lab of Microanalytical Methods & Instrumentation, Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Wang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Central Laboratory, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Tian
authors.affiliation: Beijing Tech-Sky Pharmaceutical Technology Co., Ltd, Beijing 100044, China.
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Yuan
authors.affiliation: Beijing Tech-Sky Pharmaceutical Technology Co., Ltd, Beijing 100044, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Li
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Beijing Key Lab of Microanalytical Methods & Instrumentation, Department of Chemistry, Tsinghua University, Beijing 100084, China.
authors.forename: Qiong-Lin
authors.initials: QL
authors.lastname: Liang
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Beijing Key Lab of Microanalytical Methods & Instrumentation, Department of Chemistry, Tsinghua University, Beijing 100084, China; State Key Laboratory for Quality Research in Chinese Medicines, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China. Electronic address: luoga@mail.tsinghua.edu.cn.
authors.forename: Guo-An
authors.initials: GA
authors.lastname: Luo
mesh_terms: D000284:Administration, Oral; D031403:Anemarrhena / Q000737:chemistry*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D013058:Mass Spectrometry; D059808:Polyphenols / Q000008:administration & dosage / Q000097:blood*; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D013607:Tablets
chemical_list: D059808:Polyphenols; D013607:Tablets
keywords: Anemarrhenae rhizoma; LC–MS; Mangiferin; Metabolites; Neomangiferin; Plasma pharmacokinetics; Rat; Xanthones C-glycosides