Title:Exploring Mechanisms of Houshiheisan in Treating Ischemic Stroke with
Network Pharmacology and Independent Cascade Model
Volume: 27
Issue: 7
Author(s): Bo Cao, Jiao Jin, Zhiyu Tang, Qiong Luo, Jinbing An*Wei Pang*
Affiliation:
- Department of Health Informatics and Management, School of Health Humanities, Peking University, Beijing, 100191, China
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China
Keywords:
Houshiheisan, ischemic stroke, network pharmacology, independent cascade model, molecular docking, signaling pathway.
Abstract:
Background: Houshiheisan (HSHS) has been effective in the treatment of ischemic
stroke (IS) for centuries. However, its mechanisms are still underexplored.
Objective: The objective of this study is to identify the active ingredients and mechanisms of
HSHS in treating IS.
Methods: We searched the main active compounds in HSHS and their potential targets, and key
targets related to IS. Based on the common targets of HSHS and IS, we further expanded genes by
KEGG database to obtain target genes and related genes, as well as gene interactions in the form of
A→B, and then constructed a directed network including traditional Chinese medicines (TCMs),
active compounds and genes. Finally, based on enrichment analysis, independent cascade (IC)
model, and molecular docking, we explored the mechanisms of HSHS in treating IS.
Results: A directed network with 6,348 nodes and 64,996 edges was constructed. The enrichment
analysis suggested that the AGE pathway, glucose metabolic pathway, lipid metabolic pathway, and
inflammation pathway played critical roles in the treatment of IS by HSHS. Furthermore, the gene ontologies
(GOs) of three monarch drugs in HSHS mainly involved cellular response to chemical stress,
blood coagulation, hemostasis, positive regulation of MAPK cascade, and regulation of inflammatory
response. Several candidate drug molecules were identified by molecular docking.
Conclusion: This study advocated potential drug development with targets in the AGE signaling
pathway, with emphasis on neuroprotective, anti-inflammatory, and anti-apoptotic functions. The
molecular docking simulation indicated that the ligand-target combination selection method based
on the IC model was effective and reliable.
