Analysis of the role and mechanism of EGCG in septic cardiomyopathy based on network pharmacology

PeerJ. 2022 Mar 9:10:e12994. doi: 10.7717/peerj.12994. eCollection 2022.

Abstract

Background: Septic cardiomyopathy (SC) is a common complication of sepsis that leads to an increase in mortality. The pathogenesis of septic cardiomyopathy is unclear, and there is currently no effective treatment. EGCG (epigallocatechin gallate) is a polyphenol that has anti-inflammatory, antiapoptotic, and antioxidative stress effects. However, the role of EGCG in septic cardiomyopathy is unknown.

Methods: Network pharmacology was used to predict the potential targets and molecular mechanisms of EGCG in the treatment of septic cardiomyopathy, including the construction and analysis of protein-protein interaction (PPI) network, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and molecular docking. The mouse model of septic cardiomyopathy was established after intraperitoneal injection of LPS (lipopolysaccharide). The myocardial protective effect of EGCG on septic mice is observed by cardiac ultrasound and HE staining. RT-PCR is used to verify the expression level of the EGCG target in the septic cardiomyopathy mouse model.

Results: A total of 128 anti-SC potential targets of EGCGareselected for analysis. The GO enrichment analysis and KEGG pathway analysis results indicated that the anti-SC targets of EGCG mainly participate in inflammatory and apoptosis processes. Molecular docking results suggest that EGCG has a high affinity for the crystal structure of six targets (IL-6 (interleukin-6), TNF (tumor necrosis factor), Caspase3, MAPK3 (Mitogen-activated protein kinase 3), AKT1, and VEGFA (vascular endothelial growth factor)), and the experimental verification result showed levated expression of these 6 hub targets in the LPS group, but there is an obvious decrease in expression in the LPS + EGCG group. The functional and morphological changes found by echocardiography and HE staining show that EGCG can effectively improve the cardiac function that is reduced by LPS.

Conclusion: Our results reveal that EGCG may be a potentially effective drug to improve septic cardiomyopathy. The potential mechanism by which EGCG improves myocardial injury in septic cardiomyopathy is through anti-inflammatory and anti-apoptotic effects. The anti-inflammatory and anti-apoptotic effects of EGCG occur not only through direct binding to six target proteins (IL-6,TNF-α, Caspase3, MAPK3, AKT1, and VEGFA) but also by reducing their expression.

Keywords: Apoptosis; EGCG; Inflammation; Network pharmacology; Septic cardiomyopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomyopathies* / drug therapy
  • Disease Models, Animal
  • Interleukin-6
  • Lipopolysaccharides
  • Mice
  • Molecular Docking Simulation
  • Network Pharmacology*
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A

Substances

  • epigallocatechin gallate
  • Interleukin-6
  • Lipopolysaccharides
  • Vascular Endothelial Growth Factor A
  • Tumor Necrosis Factor-alpha

Grants and funding

This work was supported by the National Natural Science Foundation of China (NO. 81860058, 81960088), and special funds for guiding local scientific and technological development by the central government of China (NO. S2019CXSFG0016). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.