A Network Pharmacology to Explore the Mechanism of Calculus Bovis in the Treatment of Ischemic Stroke

Fangchen Liu; Ling Li; Jian Chen; Ying Wu; Yongbing Cao; Ping Zhong

doi:10.1155/2021/6611018

A Network Pharmacology to Explore the Mechanism of Calculus Bovis in the Treatment of Ischemic Stroke

Biomed Res Int. 2021 Mar 10:2021:6611018. doi: 10.1155/2021/6611018. eCollection 2021.

Authors

Fangchen Liu^{1

2}, Ling Li³, Jian Chen³, Ying Wu¹, Yongbing Cao³, Ping Zhong^{1

4}

Affiliations

¹ Department of Neurology, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China.
² Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
³ Institute of Vascular Disease, Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China.
⁴ Department of Neurology, Shidong Hospital of Yangpu District, Shanghai 200090, China.

Abstract

Background: Calculus Bovis is a valuable Chinese medicine, which is widely used in the clinical treatment of ischemic stroke. The present study is aimed at investigating its target and the mechanism involved in ischemic stroke treatment by network pharmacology.

Methods: Effective compounds of Calculus Bovis were collected using methods of network pharmacology and using the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Potential compound targets were searched in the TCMSP and SwissTargetPrediction databases. Ischemic stroke-related disease targets were searched in the Drugbank, DisGeNet, OMIM, and TTD databases. These two types of targets were uploaded to the STRING database, and a network of their interaction (PPI) was built with its characteristics calculated, aiming to reveal a number of key targets. Hub genes were selected using a plug-in of the Cytoscape software, and Gene Ontology (GO) biological processes and pathway enrichment analyses of Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted using the clusterProfiler package of R language.

Results: Among 12 compounds, deoxycorticosterone, methyl cholate, and biliverdin were potentially effective components. A total of 344 Calculus Bovis compound targets and 590 ischemic stroke targets were found with 92 overlapping targets, including hub genes such as TP53, AKT, PIK2CA, MAPK3, MMP9, and MMP2. Biological functions of Calculus Bovis are associated with protein hydrolyzation, phosphorylation of serine/threonine residues of protein substrates, peptide bond hydrolyzation of peptides and proteins, hydrolyzation of intracellular second messengers, antioxidation and reduction, RNA transcription, and other biological processes.

Conclusion: Calculus Bovis may play a role in ischemic stroke by activating PI3K-AKT and MAPK signaling pathways, which are involved in regulating inflammatory response, cell apoptosis, and proliferation.

Publication types

Retracted Publication

MeSH terms

Antioxidants* / administration & dosage
Antioxidants* / chemistry
Antioxidants* / pharmacokinetics
Databases, Protein*
Drugs, Chinese Herbal* / administration & dosage
Drugs, Chinese Herbal* / chemistry
Drugs, Chinese Herbal* / pharmacokinetics
Humans
Ischemic Stroke* / drug therapy
Ischemic Stroke* / metabolism
Medicine, Chinese Traditional
Molecular Docking Simulation*
Protein Interaction Maps*

Substances

Antioxidants
Drugs, Chinese Herbal