Related Experiment Video
Updated: Jun 16, 2026
Antagonistic Effect of Jiawei Shengjiang San on a Rat Model of Diabetic Nephropathy: Related to EGFR/MAPK3/1 Signaling Pathway
Published on: May 10, 2024
Quercetin down-regulates MCP-1 expression in autoimmune myocarditis via ERK1/2-C/EBPβ pathway: An integrative
Jinlin Liu1, Zhuolun Li2, Wei Liu3
1Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Abstract:
Myocarditis is one of the common causes of sudden death in adolescents, and autoimmune response and inflammation play an essential role in the development of myocarditis. Quercetin is a natural flavonoid compound with anti-inflammatory and cardioprotective effects. However, the mechanism of quercetin in autoimmune myocarditis remains unclear. This study observed that quercetin significantly improved cardiac function, inflammation and fibrosis in mice with experimental autoimmune myocarditis (EAM). In addition, Network pharmacology predicts the key target C/EBPβ and signalling pathway MAPK for quercetin treatment of autoimmune myocarditis. CESTA and DARTS experiments verified that quercetin and C/EBPβ have strong binding ability. It is shown that quercetin down-regulates MCP-1 expression in H9C2 cells by dephosphorylation of ERK1/2 and C/EBPβ. Specifically, quercetin reduced the binding of C/EBPβ to the MCP-1 promoter, resulting in decreased expression of MCP-1, which was associated with decreased ERK1/2 dependent phosphorylation at the C/EBPβ threonine 188 site. This inhibitory effect of quercetin could be further enhanced by the ERK1/2 inhibitor PD98059. The biological relevance of this regulatory network is demonstrated in EAM mice. In conclusion, these results illustrate the protective effect of quercetin against autoimmune myocarditis. A novel regulatory mechanism was revealed, namely the down-regulation of MCP-1 through the ERK1/2-C/EBPβ axis. This provides a new therapeutic strategy for autoimmune myocarditis.
Insights
Quercetin effectively treats autoimmune myocarditis by reducing inflammation and fibrosis. It works by inhibiting the ERK1/2-C/EBPβ pathway, decreasing MCP-1 expression, offering a new therapeutic strategy.
Area of Science:
- Cardiology
- Immunology
- Pharmacology
Background:
- Autoimmune myocarditis is a significant cause of sudden death in adolescents.
- Inflammation and autoimmune responses are key factors in myocarditis development.
- Quercetin, a natural flavonoid, possesses anti-inflammatory and cardioprotective properties, but its mechanism in autoimmune myocarditis is not fully understood.
Purpose of the Study:
- To investigate the therapeutic mechanism of quercetin in experimental autoimmune myocarditis (EAM).
- To identify key molecular targets and pathways involved in quercetin's protective effects against autoimmune myocarditis.
Main Methods:
- Experimental autoimmune myocarditis (EAM) mouse model.
- Network pharmacology for target prediction.
- CESTA and DARTS assays for binding verification.
- In vitro studies using H9C2 cells.
- Inhibition of ERK1/2 pathway.
Main Results:
- Quercetin significantly improved cardiac function, reduced inflammation, and attenuated fibrosis in EAM mice.
- Network pharmacology identified C/EBPβ and the MAPK pathway as key targets.
- Quercetin down-regulated MCP-1 expression by dephosphorylating ERK1/2 and C/EBPβ, reducing C/EBPβ binding to the MCP-1 promoter.
- The inhibitory effect was linked to decreased phosphorylation at the C/EBPβ threonine 188 site and enhanced by an ERK1/2 inhibitor.
Conclusions:
- Quercetin demonstrates a protective effect against autoimmune myocarditis.
- A novel mechanism involving the down-regulation of MCP-1 via the ERK1/2-C/EBPβ axis was elucidated.
- This study provides a potential new therapeutic strategy for autoimmune myocarditis.
