Mechanism of puerarin improving myocardial contractile function in myocardial hypertrophy by inhibiting ferroptosis via Nrf2/ARE/HO-1 signaling pathway.
10.19540/j.cnki.cjcmm.20250512.503
- Author:
Yan-Dong LIU
1
;
Wei QIAO
2
;
Zhao-Hui PEI
1
;
Guo-Liang SONG
1
;
Wei JIN
1
;
Wei-Bing ZHONG
1
;
Qin-Qin DENG
1
Author Information
1. the Second Department of Cardiovascular Disease, Nanchang People's Hospital (Nanchang Third Hospital) Nanchang 330009, China.
2. Health Institute of Nanchang Normal University Nanchang 330009, China.
- Publication Type:Journal Article
- Keywords:
Nrf2/ARE/HO-1 signaling pathway;
ferroptosis;
myocardial hypertrophy;
puerarin
- MeSH:
Animals;
NF-E2-Related Factor 2/genetics*;
Rats;
Ferroptosis/drug effects*;
Signal Transduction/drug effects*;
Isoflavones/pharmacology*;
Male;
Rats, Sprague-Dawley;
Cardiomegaly/genetics*;
Myocytes, Cardiac/metabolism*;
Antioxidant Response Elements/drug effects*;
Myocardial Contraction/drug effects*;
Heme Oxygenase-1/genetics*;
Cell Line
- From:
China Journal of Chinese Materia Medica
2025;50(16):4679-4689
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to explore the specific mechanism by which puerarin inhibits ferroptosis and improves the myocardial contractile function in myocardial hypertrophy through the nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE)/heme oxygenase-1(HO-1) signaling pathway. The hypertrophic cardiomyocyte model was established using phenylephrine, and H9c2 cells were divided into control group, model group, puerarin group, and puerarin+ML385 group. Cell viability and surface area were detected by cell counting kit-8(CCK-8) and immunofluorescence experiments. The mitochondrial membrane potential and Ca~(2+) concentration were measured. The ferroptosis-related indicators were detected by biochemical and fluorescence staining methods. The expression of proteins related to ferroptosis and the Nrf2/ARE/HO-1 signaling pathway was detected by Western blot. A myocardial hypertrophy model was established, and 40 rats were randomly divided into sham group, model group, puerarin group, and puerarin+Nrf2 inhibitor(ML385) group, with 10 rats in each group. Echocardiogram, hemodynamic parameters, and myocardial hypertrophy parameters were measured. Histopathological changes of myocardial tissues were observed by hematoxylin and eosin(HE) staining and Masson staining. Biochemical methods, enzyme-linked immunosorbent assay(ELISA), and fluorescence staining were used to detect inflammatory factors and ferroptosis-related indicators. Immunohistochemistry was used to detect the expression of proteins related to ferroptosis and the Nrf2/ARE/HO-1 signaling pathway. Cell experiments showed that puerarin intervention significantly enhanced the viability of hypertrophic cardiomyocytes, reduced their surface area, and restored mitochondrial membrane potential and Ca~(2+) homeostasis. Mechanism studies revealed that puerarin promoted Nrf2 nuclear translocation, upregulated the expression of HO-1, solute carrier family 7 member 11(SLC7A11), and glutathione peroxidase 4(GPX4), and decreased malondialdehyde(MDA), reactive oxygen species(ROS), and iron levels. These protective effects were reversed by ML385. In animal experiments, puerarin improved cardiac function in rats with myocardial hypertrophy, alleviated myocardial hypertrophy and fibrosis, inhibited inflammatory responses and ferroptosis, and promoted nuclear Nrf2 translocation and HO-1 expression. However, combined intervention with ML385 led to deterioration of hemodynamics and a rebound in ferroptosis marker levels. In conclusion, puerarin may inhibit cardiomyocyte ferroptosis through the Nrf2/ARE/HO-1 signaling pathway, thereby improving myocardial contractile function in myocardial hypertrophy.
