Jianpi Qinghua Formula Alleviates Diabetic Myocardial Injury Through Inhibiting JunB/c-Fos Expression

Lin Wang1,2(), Qing-guang Chen1, Hao Lu1()

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Current Medical Science ›› 2024, Vol. 44 ›› Issue (1) : 144-155. DOI: 10.1007/s11596-024-2830-1

Jianpi Qinghua Formula Alleviates Diabetic Myocardial Injury Through Inhibiting JunB/c-Fos Expression

  • Lin Wang1,2(), Qing-guang Chen1, Hao Lu1()
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Abstract

Abstract
Objective

Diabetic cardiomyopathy (DCM) represents a substantial risk factor for heart failure and increased mortality in individuals afflicted with diabetes mellitus (DM). DCM typically manifests as myocardial fibrosis, myocardial hypertrophy, and impaired left ventricular diastolic function. While the clinical utility of the Jianpi Qinghua (JPQH) formula has been established in treating diabetes and insulin resistance, its potential efficacy in alleviating diabetic cardiomyopathy remains uncertain. This study aims to investigate the impact and underlying molecular mechanisms of the JPQH formula (JPQHF) in ameliorating myocardial injury in nonobese diabetic rats, specifically focusing on apoptosis and inflammation.

Methods

Wistar rats were assigned as the normal control group (CON), while Goto-Kakizaki (GK) rats were randomly divided into three groups: DM, DM treated with the JPQHF, and DM treated with metformin (MET). Following a 4-week treatment regimen, various biochemical markers related to glucose metabolism, cardiac function, cardiac morphology, and myocardial ultrastructure in GK rats were assessed. RNA sequencing was utilized to analyze differential gene expression and identify potential therapeutic targets. In vitro experiments involved high glucose to induce apoptosis and inflammation in H9c2 cells. Cell viability was evaluated using CCK-8 assay, apoptosis was monitored via flow cytometry, and the production of inflammatory cytokines was measured using quantitative real-time PCR (qPCR) and ELISA. Protein expression levels were determined by Western blotting analysis. The investigation also incorporated the use of MAPK inhibitors to further elucidate the mechanism at both the transcriptional and protein levels.

Results

The JPQHF group exhibited significant reductions in interventricular septal thickness at end-systole (IVSs) and left ventricular internal diameter at end-systole and end-diastole (LVIDs and LVIDd). JPQHF effectively suppressed high glucose-induced activation of IL-1β and caspase 3 in cardiomyocytes. Furthermore, JPQHF downregulated the expression of myocardial JunB/c-Fos, which was upregulated in both diabetic rats and high glucose-treated H9c2 cells.

Conclusion

The JPQH formula holds promise in mitigating diabetic myocardial apoptosis and inflammation in cardiomyocytes by inhibiting JunB/c-Fos expression through suppressing the MAPK (p38 and ERK1/2) pathway.

Keywords

Jianpi Qinghua formula / diabetic cardiomyopathy / AP-1 transcription factor / apoptosis / inflammation

Cite this article

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Lin Wang, Qing-guang Chen, Hao Lu. Jianpi Qinghua Formula Alleviates Diabetic Myocardial Injury Through Inhibiting JunB/c-Fos Expression. Current Medical Science, 2024, 44(1): 144‒155 https://doi.org/10.1007/s11596-024-2830-1

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