Title:Exploring the Constituents and Mechanisms of Polygonum multiflorum Thunb. in Mitigating Ischemic Stroke: A Network Pharmacology and Molecular Docking Study
Volume: 28
Issue: 5
Author(s): Lingyu Ruan, Mengyun Zheng, Xinru Xia, Chaofan Pang, Yating Wang, Zhiwei Fan, Jingtian Yang, Qing Qing, Hongyan Lin, Yuheng Tao, Junsong Wang*Liqun Wang*
Affiliation:
- Center of Molecular Metabolism, Nanjing University of Science and Technology, 200
Xiaolingwei Street, Nanjing, 210094, China
- School of Pharmacy and School of Biological and Food Engineering, Changzhou University, 21 GeHu Middle Road,
Changzhou, 213164, China
Keywords:
Polygonum multiflorum Thunb., ischemic stroke, network pharmacology, molecular docking, oxygen-glucose deprivation and reperfusion (OGD/R), protein-protein interaction (PPI).
Abstract:
Backgound: Polygonum multiflorum Thunb. (PMT) has shown promise in exerting
cerebrovascular protective effects, and its potential for treating ischemic stroke (IS) has garnered
attention. However, the lack of clarity regarding its chemical constituents and mechanisms has
significantly hindered its clinical application.
Methods: In this study, we employed network pharmacology and molecular docking techniques
for the first time to elucidate the potential compounds and targets of PMT in treating IS. The databases
CTD, DrugBank, DisGeNET, GeneCards, OMIM, TTD, PGKB, NCBI, TCMIP, CNKI,
PubMed, ZINC, STITCH, BATMAN, ETCM and Swiss provided information on targets related
to IS and components of PMT, along with their associated targets. We constructed “compoundtarget”
and protein-protein interaction (PPI) networks sourced from the STRING database using
the Cytoscape software. Gene Ontology (GO) enrichment analysis and KEGG pathway analysis
were conducted using the DAVID database. Molecular docking between core targets and active
compounds was conducted using Autodock4 software. Experiments were performed in an oxygen-
glucose deprivation and reperfusion (OGD/R) model to validate the anti-IS activity of compounds
isolated from PMT preliminarily. Network pharmacological analysis revealed 16 core
compounds, including resveratrol, polydatin, TSG, ω-hydroxyemodin, emodin anthrone, tricin,
moupinamide, and others, along with 11 high-degree targets, such as PTGS1, PTGS2, ADORA1,
ADORA2, CA1, EGFR, ESR1, ESR2, SRC, MMP3 and MMP9.
Results: GO and KEGG enrichment analyses revealed the involvement of HIF-1, Akt signaling
pathway and energy metabolism-related signaling pathways. Molecular docking results emphasized
eight key compounds and confirmed their interactions with corresponding targets. In vitro
OGD/R model experiments identified TSG and tricin as the primary active substances within
PMT for its anti-stroke activity.
Conclusion: This study contributes new insights into the potential development of PMT for
stroke prevention and treatment.
