PMID- 34690756
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211026
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 12
DP  - 2021
TI  - Integrated Network Pharmacology Analysis and Experimental Validation to 
      Investigate the Mechanism of Zhi-Zi-Hou-Po Decoction in Depression.
PG  - 711303
LID - 10.3389/fphar.2021.711303 [doi]
LID - 711303
AB  - Zhi-Zi-Hou-Po Decoction (ZZHPD) is a well-known traditional Chinese medicine 
      (TCM) that has been widely used in depression. However, the antidepressant 
      mechanism of ZZHPD has not yet been fully elucidated. The purpose of this study 
      was to explore the pharmacological mechanisms of ZZHPD acting on depression by 
      combining ultra flow liquid chromatography with quadrupole time-of-flight mass 
      spectrometry (UFLC-Q-TOF/MS) and network pharmacology strategy. The chemical 
      components of ZZHPD were identified using UFLC-Q-TOF/MS, while the potential drug 
      targets and depression-related targets were collected from databases on the basis 
      of the identified compounds of ZZHPD. Protein-protein interaction (PPI) network, 
      gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway 
      enrichment analyses were used to unravel potential antidepressant mechanisms. The 
      predicted antidepressant targets from the pharmacology-based analysis were 
      further verified in vivo. As a result, a total of 31 chemical compounds were 
      identified by UFLC-Q-TOF/MS; 514 promising drug targets were mined by using the 
      Swiss Target Prediction; and 527 depression-related target genes were pinpointed 
      by the GeneCards and OMIM databases. STRING database and Cytoscape's topological 
      analysis revealed 80 potential targets related to the antidepressant mechanism of 
      ZZHPD. The KEGG pathway analysis revealed that the antidepressant targets of 
      ZZHPD were mainly involved in dopaminergic synapse, serotonin synapse, cAMP, and 
      mTOR signaling pathways. Furthermore, based on the animal model of depression 
      induced by chronic corticosterone, the regulatory effects of ZZHPD on the 
      expression of MAOA, MAOB, DRD2, CREBBP, AKT1, MAPK1, HTR1A, and GRIN2B mRNA 
      levels as well as the cAMP signaling pathway and monoaminergic metabolism were 
      experimentally verified in rats. Our study revealed that ZZHPD is expounded to 
      target various genes and pathways to perform its antidepressant effect.
CI  - Copyright (c) 2021 Bai, Zhang, Li, Zhang, Wang, He and Ju.
FAU - Bai, Yongtao
AU  - Bai Y
AD  - Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University, Henan 
      Cancer Hospital, Zhengzhou, China.
AD  - Phase I Clinical Research Center, Affiliated Cancer Hospital of Zhengzhou 
      University, Henan Cancer Hospital, Zhengzhou, China.
FAU - Zhang, Yingchun
AU  - Zhang Y
AD  - College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, 
      Chongqing, China.
FAU - Li, Shuolei
AU  - Li S
AD  - Phase I Clinical Research Center, Affiliated Cancer Hospital of Zhengzhou 
      University, Henan Cancer Hospital, Zhengzhou, China.
FAU - Zhang, Wenzhou
AU  - Zhang W
AD  - Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University, Henan 
      Cancer Hospital, Zhengzhou, China.
FAU - Wang, Xinhui
AU  - Wang X
AD  - College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, 
      Chongqing, China.
FAU - He, Baoxia
AU  - He B
AD  - Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University, Henan 
      Cancer Hospital, Zhengzhou, China.
AD  - Phase I Clinical Research Center, Affiliated Cancer Hospital of Zhengzhou 
      University, Henan Cancer Hospital, Zhengzhou, China.
FAU - Ju, Wenzheng
AU  - Ju W
AD  - Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of 
      Chinese Medicine, Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20211008
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC8531485
OTO - NOTNLM
OT  - CAMP signaling pathway
OT  - UFLC-Q-TOF/MS
OT  - Zhi-Zi-Hou-Po decoction
OT  - depression
OT  - network pharmacology
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/10/26 06:00
MHDA- 2021/10/26 06:01
PMCR- 2021/10/08
CRDT- 2021/10/25 06:23
PHST- 2021/05/18 00:00 [received]
PHST- 2021/09/07 00:00 [accepted]
PHST- 2021/10/25 06:23 [entrez]
PHST- 2021/10/26 06:00 [pubmed]
PHST- 2021/10/26 06:01 [medline]
PHST- 2021/10/08 00:00 [pmc-release]
AID - 711303 [pii]
AID - 10.3389/fphar.2021.711303 [doi]
PST - epublish
SO  - Front Pharmacol. 2021 Oct 8;12:711303. doi: 10.3389/fphar.2021.711303. 
      eCollection 2021.