Abstract
The incidence of heart failure was significantly increased in patients with diabetic cardiomyopathy (DCM). The therapeutic effect of triptolide on DCM has been reported, but the underlying mechanisms remain to be elucidated. This study is aimed at investigating the potential targets of triptolide as a therapeutic strategy for DCM using a network pharmacology approach. Triptolide and its targets were identified by the Traditional Chinese Medicine Systems Pharmacology database. DCM-associated protein targets were identified using the comparative toxicogenomics database and the GeneCards database. The networks of triptolide-target genes and DCM-associated target genes were created by Cytoscape. The common targets and enriched pathways were identified by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The gene-gene interaction network was analyzed by the GeneMANIA database. The drug-target-pathway network was constructed by Cytoscape. Six candidate protein targets were identified in both triptolide target network and DCM-associated network: STAT3, VEGFA, FOS, TNF, TP53, and TGFB1. The gene-gene interaction based on the targets of triptolide in DCM revealed the interaction of these targets. Additionally, five key targets that were linked to more than three genes were determined as crucial genes. The GO analysis identified 10 biological processes, 2 cellular components, and 10 molecular functions. The KEGG analysis identified 10 signaling pathways. The docking analysis showed that triptolide fits in the binding pockets of all six candidate targets. In conclusion, the present study explored the potential targets and signaling pathways of triptolide as a treatment for DCM. These results illustrate the mechanism of action of triptolide as an anti-DCM agent and contribute to a better understanding of triptolide as a transcriptional regulator of cytokine mRNA expression.
Highlights
Diabetic cardiomyopathy (DCM) is defined as abnormal cardiac structure and function in the absence of other cardiac risk factors [1]
We found that triptolide had high oral bioavailability (OB) and drug likeness (DL)
Six core potential targets (STAT3, VEGFA, FOS, TNF, TP53, and TGFB1) of triptolide in the treatment of DCM are identified by network pharmacology
Summary
Diabetic cardiomyopathy (DCM) is defined as abnormal cardiac structure and function in the absence of other cardiac risk factors [1]. DCM has been well studied in the past decades, it remains a significant cause of morbidity and mortality in patients with diabetes [2]. A growing number of studies have shown that diverse mechanisms are involved in diabetes-associated cardiac dysfunction, including systemic insulin resistance, oxidative stress, inflammation, activation of the renin angiotensin aldosterone system, and dysregulation of the immune system [3]. The management of high blood glucose levels in patients with DCM is tailored to minimize the risk of cardiovascular complications [4]. Western drugs can reduce the risk of cardiac complications without the blood glucose-. Target prediction TCMSP Cytoscape CTD Gene cards Common targets. Enrichment analysis Gene mania Web gestalt GO KEGG
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