Analysis of the role and mechanism of EGCG in septic cardiomyopathy based on network pharmacology
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, antiapopto...
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PeerJ Inc.
2022-03-01
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| Online Access: | https://peerj.com/articles/12994.pdf |
| _version_ | 1797420146705301504 |
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| author | Ji Wu Zhenhua Wang Shanling Xu Yang Fu Yi Gao Zuxiang Wu Yun Yu Yougen Yuan Lin Zhou Ping Li |
| author_facet | Ji Wu Zhenhua Wang Shanling Xu Yang Fu Yi Gao Zuxiang Wu Yun Yu Yougen Yuan Lin Zhou Ping Li |
| author_sort | Ji Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T06:57:27Z |
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| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:57:27Z |
| publishDate | 2022-03-01 |
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| spelling | doaj.art-b05637749ec34383a190d090485d184e2023-12-03T10:02:36ZengPeerJ Inc.PeerJ2167-83592022-03-0110e1299410.7717/peerj.12994Analysis of the role and mechanism of EGCG in septic cardiomyopathy based on network pharmacologyJi Wu0Zhenhua Wang1Shanling Xu2Yang Fu3Yi Gao4Zuxiang Wu5Yun Yu6Yougen Yuan7Lin Zhou8Ping Li9Department of Cardiovascular, The Second Affiliated Hospital of Nanchang University, Nan Chang, ChinaDepartment of Cardiovascular, The Second Affiliated Hospital of Nanchang University, Nan Chang, ChinaDepartment of Cardiovascular, Medicine, Fuzhou First People’s Hospital, Fu Zhou, ChinaDepartment of Cardiovascular, The Second Affiliated Hospital of Nanchang University, Nan Chang, ChinaDepartment of Cardiovascular, The Second Affiliated Hospital of Nanchang University, Nan Chang, ChinaDepartment of Cardiovascular, The Second Affiliated Hospital of Nanchang University, Nan Chang, ChinaDepartment of Cardiovascular, The Second Affiliated Hospital of Nanchang University, Nan Chang, ChinaDepartment of Cardiovascular, The Three Affiliated Hospital of Nanchang University, Nan Chang, ChinaDepartment of Cardiovascular, The Three Affiliated Hospital of Nanchang University, Nan Chang, ChinaDepartment of Cardiovascular, The Second Affiliated Hospital of Nanchang University, Nan Chang, ChinaBackground 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.https://peerj.com/articles/12994.pdfEGCGSeptic cardiomyopathyNetwork pharmacologyInflammationApoptosis |
| spellingShingle | Ji Wu Zhenhua Wang Shanling Xu Yang Fu Yi Gao Zuxiang Wu Yun Yu Yougen Yuan Lin Zhou Ping Li Analysis of the role and mechanism of EGCG in septic cardiomyopathy based on network pharmacology PeerJ EGCG Septic cardiomyopathy Network pharmacology Inflammation Apoptosis |
| title | Analysis of the role and mechanism of EGCG in septic cardiomyopathy based on network pharmacology |
| title_full | Analysis of the role and mechanism of EGCG in septic cardiomyopathy based on network pharmacology |
| title_fullStr | Analysis of the role and mechanism of EGCG in septic cardiomyopathy based on network pharmacology |
| title_full_unstemmed | Analysis of the role and mechanism of EGCG in septic cardiomyopathy based on network pharmacology |
| title_short | Analysis of the role and mechanism of EGCG in septic cardiomyopathy based on network pharmacology |
| title_sort | analysis of the role and mechanism of egcg in septic cardiomyopathy based on network pharmacology |
| topic | EGCG Septic cardiomyopathy Network pharmacology Inflammation Apoptosis |
| url | https://peerj.com/articles/12994.pdf |
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