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Cyanidin prevents cardiomyocyte apoptosis in mice after myocardial infarction

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Abstract

Myocardial infarction is a worldwide disease with high morbidity and mortality and a major cause of chronic heart failure, seriously affecting patients’ quality of life. Natural medicine has been used to cure or prevent cardiovascular disease for decades. As a natural flavonoid, anthocyanidin has been used to treat many diseases due to its antioxidative, anti-inflammatory, and other properties. A mouse model (C57BL/6) weighing 30–40 g was utilized to induce myocardial infarction by ligating the left anterior descending coronary artery. Cyanidin (30 mg/kg) was administered orally to mice for four weeks. A variety of assessments were used to evaluate cardiac function. The gene expression was measured using RNAseq and Western blot. Histological changes in myocardial tissue were assessed using staining techniques, including Masson, Hematoxylin Eosin (HE), and transmission electron microscopy. Tunnel staining was implemented as a method to detect cellular apoptosis. For the quantification of B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in the serum, an enzyme-linked immunosorbent assay (ELISA) was employed. Furthermore, autodock simulation was executed in order to assess the interaction between cyanidin and a subset of genes. Cyanidin treatment inhibited myocardial cell apoptosis, improved cardiac function, and reduced serum concentrations of BNP and atrial natriuretic peptide ANP, as well as mitigated histological cardiac tissue damage. Cyanidin also inhibited the activity of matrix metalloproteinases (MMP2/9) and Fibronectin 1 (Fn1). Cyanidin improves heart function and reduces myocardial damage in mice after MI. Furthermore, cyanidin can prevent cardiomyocyte apoptosis. These effects are most likely caused by suppression of MMP9/2 and control of the Akt signaling pathway, suggesting an appropriate therapeutic target.

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Data availability

No datasets were generated or analysed during the current study.

Abbreviations

Akt:

Protein kinase B

Col:

Collagen

Cyn:

Cyanidin

DEGs:

Differentially expressed genes

ECG:

Electrocardiogram

FN:

Fibronectin

GO:

Gene ontology

HE:

Hematoxylin and eosin

qPCR:

Quantitative real-time quantitative

LVEF:

Left ventricular ejection fraction

MMP:

Matrix metalloproteinases

RMSD:

Means square deviation

MI:

Myocardial infarction

OCT:

Optical coherence tomography

PPI:

Protein-protein interaction

TGF-β:

Transforming growth factor beta

UV:

Ultraviolet

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Funding

This research was funded by the National Key Research and Development Program of China (2017YFA010560, 22018YFA0108700), the NSFC Projects of International Cooperation and Exchanges (81720108004), the National Natural Science Foundation of China (81974019), the Research Team Project of Natural Science Foundation of Guangdong Province of China (2017A030312007), the Key Program of Guangzhou Science Research Plan (201904020047), the Special Projects of Dengfeng Program of Guangdong Provincial People’s Hospital (DFJH201812, KJ012019119, KJ012020630, KJ012019423, KY0120220133, DFJHBF202111, KJ012020630), and the National Natural Science Foundation of China (82001301).

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Author notes

  1. Deng Gang, Ouyang Qing, and Yongzheng Yang have contributed equally as first authors for this manucript.

Authors and Affiliations

  1. School of Medicine, South China University of Technology, Guangzhou, 510006, People’s Republic of China

    Deng Gang, Ouyang Qing & ** Zhu

  2. Department of Cardiac Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangdong Cardiovascular Institute, Guangzhou, Guangdong, 510100, People’s Republic of China

    Deng Gang, Ouyang Qing, Yongzheng Yang, Muqaddas Masood, Yu-Hong Wang, Jiang Linhui, Su Haotao, Ge Li, Chi Liu, Moussa Ide Nasser & ** Zhu

  3. The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China

    Deng Gang, Yongzheng Yang & ** Zhu

  4. Guangdong Provincial Key Laboratory of Pathogenesis, Targeted Prevention and Treatment of Heart Disease, 106 Zhongshan Er Road, Guangzhou, 510080, People’s Republic of China

    Ouyang Qing, Yongzheng Yang, Yu-Hong Wang, Jiang Linhui, Su Haotao, Ge Li, Moussa Ide Nasser & ** Zhu

  5. Center for Discovery and Innovation, Hackensack University Medicial Center, Nutley, NJ, USA

    Muqaddas Masood

  6. Department of Nephrology, Sichuan Academy of Medical Science and Sichuan, Provincial People’s Hospital, Sichuan Renal Disease Clinical Research Center, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China

    Chi Liu

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Contributions

All authors declare that all data were generated in-house and that no paper mill was used. Conceptualization: MIN,DG; investigation MIN, DG, SZ, MM, YR, OY original draft preparation MIN, SX, LG, ZM, NL, GL, CL; review and editingMIN, MM, GL, CL; funding acquisition MIN, PZ.

Corresponding authors

Correspondence to Chi Liu, Moussa Ide Nasser or ** Zhu.

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Ethics approval

The experiment was conducted after an animal ethical review by the Guangdong Provincial People’s Hospital of the Guangdong Academy of Medical Sciences (2019492A(R2)).

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The authors declare no competing interests.

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Supplementary Information

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210_2024_2975_MOESM1_ESM.jpg

Supplementary file1 (JPG 1241 KB) Supplementary Figure 1: mRNA expression of  TGF-β, Col I, MMP-2/9, FN1  p-pi3k, p-Akt, p-mTOR compared to 18S. Each experience was repeated 3 times ****P<0.0005.

210_2024_2975_MOESM2_ESM.jpg

Supplementary file2 (JPG 1818 KB) Supplementary Figure 2: RMSF curve represents the fluctuation of protein amino acid residues. (A) The figure demonstrates that many smaller locations inside the core of the protein have more flexibility in comparison to other parts. (B) The graph demonstrates that some of these smaller regions within the core structure of the protein are more flexible than other areas. (C) As can be observed from the figure, the total residue of the protein changes less, and this is because the protein has a very compact barrel-shaped structure. Because of this, the amino acid is bound, and as a result, it swings less. (D) As the image on the right demonstrates, this region is dominated by a loop, which causes it to exhibit variability.

Supplementary file3 (PDF 443 KB)

Supplementary file4 (PDF 437 KB)

Supplementary file5 (PDF 774 KB)

Supplementary file6 (DOCX 26 KB)

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Gang, D., Qing, O., Yang, Y. et al. Cyanidin prevents cardiomyocyte apoptosis in mice after myocardial infarction. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-02975-2

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