Affiliation:
1. School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang, China
2. NMPA Key Laboratory
of Quality Evaluation of Traditional Chinese Patent Medicine, Jiangxi Institute for Drug Control, Nanchang,
China
3. Translational Medicine Centre, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
Abstract
Background:
Buyang Huanwu Decoction (BHD) is used to regulate blood circulation and
clear collaterals and is widely used in coronary heart disease. However, the active compounds
and the mechanism of BHD used to treat restenosis are less understood.
Objective:
The study aimed to explore the potential mechanism of Buyang Huanwu decoction
BHD for the treatment of restenosis using network pharmacology and molecular docking experiments.
Methods:
The bioactive components of BHD and their corresponding targets were retrieved
from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Encyclopaedia
of Traditional Chinese Medicine (ETCM) databases as well as literature. Restenosisassociated
therapeutic genes were identified from the OMIM, Drugbank, GEO, and Dis-
GeNET databases. Genes related to the vascular smooth muscle cell (VSMC) phenotype
were obtained from the gene ontology (GO) database and literature. The core target genes
for the drug-disease-VSMC phenotype were identified using the Venn tool and Cytoscape
software. Moreover, the “drug-component-target-pathway” network was constructed and
analyzed, and pathway enrichment analysis was performed. The connection between the main
active components and core targets was analyzed using the AutoDock tool, and PyMOL was
used to visualize the results.
Result:
The “compound-target-disease” network included 80 active ingredients and 599
overlapping targets. Among the bioactive components, quercetin, ligustrazine, ligustilide, hydroxysafflor
yellow A, and dihydrocapsaicin had high degree values, and the core targets
included TP53, MYC, APP, UBC, JUN, EP300, TGFB1, UBB, SP1, MAPK1,
SMAD2, CTNNB1, FOXO3, PIN1, EGR1, TCF4, FOS, SMAD3, and CREBBP. A total
of 365 items were obtained from the GO functional enrichment analysis (p < 0.05), whereas
the enrichment analysis of the KEGG pathway identified 30 signaling pathways (p < 0.05),
which involved the TGF-β signaling pathway, Wnt signaling pathway, TRAF6-mediated induction
of NF-κB and MAPK pathway, TLR7/8 cascade, and others. The molecular docking
results revealed quercetin, luteolin, and ligustilide to have good affinity with the core targets
MYC and TP53.
Conclusion:
The active ingredients in BHD might act on TP53, MYC, APP, UBC, JUN, and
other targets through its active components (such as quercetin, ligustrazine, ligustilide, hydroxysafflor
yellow A, and dihydrocapsaicin). This action of BHD may be transmitted via the
involvement of multiple signaling pathways, including the TGF-β signaling pathway, Wnt signaling
pathway, TRAF6-mediated induction of NF-κB and MAPK pathway, and TLR7/8 cascade,
to treat restenosis by inhibiting the phenotype switching and proliferation of VSMC.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangxi Province
Jiangxi Science and Technology Normal University
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,Molecular Medicine,General Medicine
Reference62 articles.
1. Hajar R.; Coronary heart disease: From mummies to 21st century. Heart views 2017,18(2),68-74
2. Siontis G.C.M.; Piccolo R.; Praz F.; Valgimigli M.; Räber L.; Mavridis D.; Jüni P.; Windecker S.; Percutaneous coronary interventions for the treatment of stenoses in small coronary arteries. JACC Cardiovasc Interv 2016,9(13),1324-1334
3. Zheng D.; Mingyue Z.; Wei S.; Min L.; Wanhong C.; Qiliang D.; Yongjun J.; Xinfeng L.; The incidence and risk factors of instent restenosis for vertebrobasilar artery stenting. World Neurosurg 2018,110,e937-e941
4. Zhang J.; Gao F.; Ni T.; Lu W.; Lin N.; Zhang C.; Sun Z.; Guo H.; Chi J.; Linc-POU3F3 is overexpressed in in-stent restenosis patients and induces VSMC phenotypic transformation via POU3F3/miR-449a/KLF4 signaling pathway. Am J Transl Res 2019,11(7),4481-4490
5. Qi Y.; Dai F.; Gu J.; Yao W.; Biomarkers in VSMC phenotypic modulation and vascular remodeling. Pharmazie 2019,74(12),711-714