Volume 11 Issue 1
Feb.  2021
Turn off MathJax
Article Contents
Lu Wang, Sen Li, Jiaxin Li, Zhongzhe Cheng, Yulin Feng, Hui Ouyang, Zhifeng Du, Hongliang Jiang. Comprehensive metabolic profiling of Alismatis Rhizoma triterpenes in rats based on characteristic ions and a triterpene database[J]. Journal of Pharmaceutical Analysis, 2021, 11(1): 96-107. doi: 10.1016/j.jpha.2020.03.010
Citation: Lu Wang, Sen Li, Jiaxin Li, Zhongzhe Cheng, Yulin Feng, Hui Ouyang, Zhifeng Du, Hongliang Jiang. Comprehensive metabolic profiling of Alismatis Rhizoma triterpenes in rats based on characteristic ions and a triterpene database[J]. Journal of Pharmaceutical Analysis, 2021, 11(1): 96-107. doi: 10.1016/j.jpha.2020.03.010

Comprehensive metabolic profiling of Alismatis Rhizoma triterpenes in rats based on characteristic ions and a triterpene database

doi: 10.1016/j.jpha.2020.03.010
Funds:

This study was financially supported by the National Natural Science Foundation of China (Grant No. 81803717 and U1603104).

  • Received Date: Oct. 27, 2019
  • Accepted Date: Mar. 21, 2020
  • Rev Recd Date: Mar. 20, 2020
  • Available Online: Jan. 24, 2022
  • Publish Date: Feb. 15, 2021
  • Alismatis Rhizoma (AR) is widely used in Chinese medicine, and its major bioactive components, triterpenes, reportedly possess various pharmacological activities. Therefore, it is very important to study the metabolism of triterpenes in vivo. However, the metabolism of AR triterpene extract has not been comprehensively elucidated due to its complex chemical components and metabolic pathways. In this study, an ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry method, which was based on the characteristic ions from an established database of known triterpenes, was used to analyze the major metabolites in rats following the oral administration of Alismatis Rhizoma extracts (ARE). As a result, a total of 233 constituents, with 85 prototype compounds and 148 metabolites, were identified for the first time. Hydrogenation, oxidation, sulfate and glucuronidation conjugation were the major metabolic pathways for triterpenes in AR. In addition, the mutual in vivo transformation of known ARE triterpenes was discovered and confirmed for the first time. Those results provide comprehensive insights into the metabolism of AR in vivo, which will be useful for future studies on its pharmacodynamics and pharmacokinetics. Moreover, this established strategy may be useful in metabolic studies of similar compounds.
  • loading
  • D.Q. Chen, Y.L. Feng, T. Tian, et al., Diuretic and anti-diuretic activities of fractions of Alismatis rhizoma, J. Ethnopharmacol. 157 (2014) 114-118
    Y.J. Chu, H.Q. Jiang, J.Q. Ju, et al., A metabolomic study using HPLC-TOF/MS coupled with ingenuity pathway analysis: Intervention effects of Rhizoma Alismatis on spontaneous hypertensive rats, J. Pharm. Biomed. Anal. 117 (2016) 446-452
    T. Tian, H. Chen, Y.Y. Zhao, Traditional uses, phytochemistry, pharmacology, toxicology and quality control of Alisma orientale (Sam.) Juzep: A review, J. Ethnopharmacol. 158 (2014) 373-387
    H.G. Jin, Q. Jin, A.R. Kim, et al., A new triterpenoid from Alisma orientale and their antibacterial effect, Arch. Pharm. Res. 35 (2012) 1919-1926
    M. Zhao, L.J. Xu, C.T. Che, Alisolide, alisols O and P from the rhizome of Alisma orientale, Phytochemistry 69 (2007) 527-532
    Y.L. Zhu, G.P. Peng, Progress in the study on chemical constituents of Alisma Orientalis, Nat. Prod. Res. Develop. 18 (2006) 348-351
    Q. Li, H. Qu, Study on the hypoglycemic activities and metabolism of alcohol extract of Alismatis Rhizoma, Fitoterapia 83 (2012) 1046-1053
    S. Li, S.N. Jin, C.W. Song, et al., The metabolic change of serum lysophosphatidylcholines involved in the lipid lowering effect of triterpenes from Alismatis rhizoma on high-fat diet induced hyperlipidemia mice, J. Ethnopharmacol. 177 (2016) 10-18
    J. Chen, Y. Song, X. Guo, et al., Characterization of the herb-derived components in rats following oral administration of Carthamus tinctorius extract by extracting diagnostic fragment ions (DFIs) in the MSn chromatograms, Analyst 139 (2014) 6474-6485
    H.M. Li, X.J. Chen, D. Luo, et al., Protostane-Type Triterpenoids from Alisma orientale, Chem. Biodivers. 14 (2017) 1-13
    S. Li, S.N. Jin, C.W. Song, et al., The strategy for establishment of the multiple reaction monitoring based characteristic chemical profile of triterpenes in Alismatis rhizoma using two combined tandem mass spectrometers, J. Chromatogr. A 1524 (2017) 121-134
    G.F. Feng, S. Liu, Z.F. Pi, et al., Comprehensive characterization of in vivo metabolic profile of Polygalae radix based on ultra-high-performance liquid chromatography-tandem mass spectrometry, J. Pharm. Biomed. Anal. 165 (2019) 173-181
    X.N. Zhang, Y. Song, Q. Jia, et al., Simultaneous determination of 58 pesticides and relevant metabolites in eggs with a multi-functional filter by ultra-high performance liquid chromatography-tandem mass spectrometry, J. Chromatogr. A 1593 (2019) 81-90
    J.M. Hur, J.W. Choi, J.C. Park, Effects of Methanol Extract of Alisma orientale Rhizome and its Major Component, Alisol B 23-acetate, on Hepatic Drug Metabolizing Enzymes in Rats Treated with Bromobenzene, Arch. Pharm. Res. 30 (2007) 1543-1549
    Z.P. Mai, X.L. Xin, Z. Sun, et al., Biotransformation of alisol G by Penicillium janthinellum and the hCE2 inhibitory effects of its metabolites, Phytochem. Lett. 13 (2015) 228-233
    W. Xu, X. Li, N. Lin, et al., Pharmacokinetics and tissue distribution of five major triterpenoids after oral administration of Rhizoma Alismatis extract to rats using ultra high-performance liquid chromatography-tandem mass spectrometry, J. Pharm. Biomed. Anal. 146 (2017) 314-323
    Y. Yu, Z.Z. Liu, P. Ju, et al., In vitro metabolism of alisol A and its metabolites’ identification using high-performance liquid chromatography-mass spectrometry, J. Chromatogr. B 941 (2013) 31-37
    S.G. Ma, S.K. Chowdhury, K.B. Alton, Application of Mass Spectrometry for Metabolite Identification, Curr. Drug Metab. 7 (2006) 503-523
    S.L. Zeng, L. Duan, B.Z. Chen, et al., Chemicalome and metabolome profiling of polymethoxylated flavonoids in Citri Reticulatae Pericarpium based on an integrated strategy combining background subtraction and modified mass defect filter in a Microsoft Excel Platform, J. Chromatogr. A 1508 (2017) 106-120
    Y.X. Zhong, X.L. Jin, S.Y. Gu, et al., Integrated identification, qualification and quantification strategy for pharmacokinetic profile study of Guizhi Fuling capsule in healthy volunteers, Sci. Rep. 6 (2016) 1-9
    M.L. Huang, Z.Z. Cheng, L. Wang, et al., A targeted strategy to identify untargeted metabolites from in vitro to in vivo: Rapid and sensitive metabolites profiling of licorice in rats using ultra-high performance liquid chromatography coupled with triple quadrupole-linear ion trap mass spectrometry, J. Chromatogr. B 1092 (2018) 40-50
    J. Liang, F. Xu, Y.Z. Zhang, et al., The profiling and identification of the absorbed constituents and metabolites of Paeoniae Radix Rubra decoction in rat plasma and urine by the HPLC-DAD-ESI-IT-TOF-MS(n) technique: a novel strategy for the systematic screening and identification of absorbed constituents and metabolites from traditional Chinese medicines, J. Pharm. Biomed. Anal. 83 (2013) 108-121
    X. Qiao, R. Li, W. Song, et al., A targeted strategy to analyze untargeted mass spectral data: Rapid chemical profiling of Scutellaria baicalensis using ultra-high performance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry and key ion filtering, J. Chromatogr. A 1441 (2016) 83-95
    Y.T. Chen, X. Feng, L.Y. Li, et al., UHPLC-Q-TOF-MS/MS method based on four-step strategy for metabolites of hinokiflavone in vivo and in vitro, J. Pharm. Biomed. Anal. 169 (2019) 19-29
    M.Q. Huang, W. Xu, S.S. Wu, et al., A 90-day subchronic oral toxicity study of triterpene-enriched extract from Alismatis Rhizoma in rats, Food Chem. Toxicol. 58 (2013) 318-323
    C.R. Cheng, M. Yang, K.T. Yu, et al., Identification of metabolites of ganoderic acid D by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry, Drug Metab. Dispos. 40 (2012) 2307-2314
    Z.H. Cheng, C.G. Ding, Z. Li, et al., Simultaneous determination of three triterpenes in rat plasma by LC-MS/MS and its application to a pharmacokinetic study of Rhizoma Alismatis extract, J. Chromatogr. B 1008 (2016) 32-37
    X.Y. Duan, J.B. Wang, X.L. Yin, et al., A 60-day feeding study of Rhizoma Alismatis Orientalis in SD rats, Chinese J. Food Hyg. 16 (2004) 108-111
    Y. Huang, S.L. Zheng, Z.S. Xu, et al., Effects of Alismatis rhizome on rat cytochrome P450 enzymes, Pharm. biol. 52 (2014) 681-687
    C.F. Wang, L. Ma, X.F. Hou, et al., Study on nephrotoxicity of ethanol extract from Alismatis Rhizoma in rats and its molecular mechanism, China J. Chinese Mater. Med. 18 (2016) 3432-3438
    J.H. Zhu, X.R. Bao, H.P. He, et al., Experimental studies of nephrotoxicity induced by Alisma orientalis in rats, Pharmacol. Clin. Chinese Mater. Med. 23 (2007) 60-62
    F. Xu, H. Yu, C. Lu, et al., The Cholesterol-Lowering Effect of Alisol Acetates Based on HMG-CoA Reductase and Its Molecular Mechanism, Evid. Based Complement. Alternat. Med. 2016 (2016) 1-11
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (63) PDF downloads(14) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return