Affiliation:
1. School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610000, P.R. China
2. Department of
Chemistry and Biochemistry, Northern Arizona University, Flagstaff, AZ, 86001, USA
3. School of Basic Medicine,
Chengdu University of Traditional Chinese Medicine, Chengdu, 611130, P.R. China
Abstract
Background and Objective:
Depressive disorder (DD) is a common chronic and highly
disabling disease. Polygoni Multiflori Caulis (PMC), a traditional Chinese medicine, has been
listed in the 2020 edition of the Chinese Pharmacopoeia. Here, the antidepressant effects and
mechanisms of PMC were explored for the first time.
Methods:
We observed the safety of PMC at a 10-fold clinically equivalent dose. Depressed mice
were induced by chronic unpredictable mild stress (CUMS) and were used to evaluate the antidepressant
effects of PMC via the sucrose preference test and the tail suspension test. The composition
of PMC was identified by ultra-high performance liquid chromatography coupled with quadrupole
exactive orbitrap mass spectrometer, and the active components, important targets, and potential
mechanism of PMC in DD treatment were predicted via network pharmacology. Investigation
included active compounds and DD-related targets screening, Gene Ontology (GO) analysis,
Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, PMC-compound-target-pathway-
DD network construction, and Molecular docking.
Results:
In the safety evaluation of PMC, no toxic side effects or deaths occurred. There were no
significant differences in liver function (ALT, AST, and TP; P > 0.05) and kidney function (BUN,
CRE, and UA; P > 0.05) in each group of mice. Compared to the control group, the model group
of mice showed significantly decreased sucrose preference and significantly increased immobility
time (P < 0.01 or P < 0.05). Compared with the model group, the mice in the PMC low, medium,
and high dose groups showed a significant decrease in immobility time and a significant increase
in sucrose preference. In the PMC-Compound-Target-Pathway-DD network, 54 active compounds,
83 common targets, and 13 major signaling pathways were identified for the treatment of DD. Molecular
docking verified that the active compounds could effectively bind with the hub targets.
Conclusion:
PMC is a relatively safe antidepressant herbal medicine with its potential mechanism
involving multiple compounds, targets, and pathways.
Publisher
Bentham Science Publishers Ltd.
Subject
Organic Chemistry,Computer Science Applications,Drug Discovery,General Medicine