PMID- 32163901
OWN - NLM
STAT- MEDLINE
DCOM- 20200625
LR  - 20200625
IS  - 1873-376X (Electronic)
IS  - 1570-0232 (Linking)
VI  - 1142
DP  - 2020 Apr 1
TI  - A novel insight into the potential toxicity mechanisms of Zhi-Zi-Hou-Po decoction 
      by dynamic urinary metabolomics based on UHPLC-Q-Exactive Orbitrap-MS.
PG  - 122019
LID - S1570-0232(19)31341-8 [pii]
LID - 10.1016/j.jchromb.2020.122019 [doi]
AB  - In recent years, depression occurs frequently. Given the long duration of the 
      disease and the high risk of recurrence, the treatment of depression requires 
      long-term medication. Zhi-Zi-Hou-Po Decoction (ZZHPD) has been used in clinical 
      treatment of depression and related diseases for many years, and the potential 
      toxic damage caused by its long-term use has gradually emerged. Existing research 
      methods that expose toxicity by a one-time administration of large doses cannot 
      provide a reference for clinical safe drug use. In this study, the potential 
      toxicity of ZZHPD in repeated administration was studied by urinary metabolomics 
      with nondestructive sampling. Based on ultra-high performance liquid 
      chromatography-quadruple-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive 
      Orbitrap-MS) and chemometrics, 33 differential biomarkers, such as 
      3-hydroxybutyric acid, indole sulfuric acid, hippuric acid and citric acid, were 
      screened and dynamically tracked. The changes of some endogenous substances 
      showed obvious time dependence. Further analysis of these time-dependent 
      components in combination with network pharmacology revealed that the potential 
      hepatotoxicity and nephrotoxicity of ZZHPD were related to the disorders of amino 
      acid metabolism, energy metabolism, lipid metabolism, nucleotide metabolism and 
      gut microflora metabolism pathway. This study can better grasp the occurrence and 
      development of drug toxicity, and provide reference for rational and safe drug 
      use and potential toxicity prevention of ZZHPD.
CI  - Copyright (c) 2020. Published by Elsevier B.V.
FAU - Zhang, Qianqian
AU  - Zhang Q
AD  - Key Laboratory of Drug Quality Control and Pharmacovigilance (China 
      Pharmaceutical University), Ministry of Education, Nanjing 210009, China; 
      Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 
      210009, China. Electronic address: qianqianzhang618@163.com.
FAU - Feng, Fang
AU  - Feng F
AD  - Key Laboratory of Drug Quality Control and Pharmacovigilance (China 
      Pharmaceutical University), Ministry of Education, Nanjing 210009, China; 
      Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 
      210009, China. Electronic address: fengfang1@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20200203
PL  - Netherlands
TA  - J Chromatogr B Analyt Technol Biomed Life Sci
JT  - Journal of chromatography. B, Analytical technologies in the biomedical and life 
      sciences
JID - 101139554
RN  - 0 (Antidepressive Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (Iridoids)
RN  - 0 (Zhi-Zi-Hou-Pu decoction)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents/adverse effects/*pharmacokinetics/urine
MH  - Biomarkers/urine
MH  - Chromatography, High Pressure Liquid
MH  - Drugs, Chinese Herbal/adverse effects/*pharmacokinetics
MH  - Iridoids/adverse effects/*pharmacokinetics/urine
MH  - Male
MH  - Metabolomics
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - Tandem Mass Spectrometry
OTO - NOTNLM
OT  - Dynamic
OT  - Potential toxicity
OT  - UHPLC-Q-Exactive Orbitrap-MS
OT  - Urinary metabolomics
OT  - Zhi-Zi-Hou-Po decoction
COIS- Declaration of Competing Interest The authors declare that there are no conflicts 
      of interest in relation to this work.
EDAT- 2020/03/13 06:00
MHDA- 2020/06/26 06:00
CRDT- 2020/03/13 06:00
PHST- 2019/09/07 00:00 [received]
PHST- 2019/12/09 00:00 [revised]
PHST- 2020/02/02 00:00 [accepted]
PHST- 2020/03/13 06:00 [pubmed]
PHST- 2020/06/26 06:00 [medline]
PHST- 2020/03/13 06:00 [entrez]
AID - S1570-0232(19)31341-8 [pii]
AID - 10.1016/j.jchromb.2020.122019 [doi]
PST - ppublish
SO  - J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Apr 1;1142:122019. doi: 
      10.1016/j.jchromb.2020.122019. Epub 2020 Feb 3.