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Protective Role of Polyphenols in Heart Failure: Molecular Targets and Cellular Mechanisms Underlying Their Therapeutic Potential.

ABSTRACT: Heart failure (HF) is a leading cause of death in the United States, with a 5-year mortality rate of 50% despite modern pharmacological therapies. Plant-based diets are comprised of a diverse polyphenol profile, which lends to their association with reduced cardiovascular disease risk. Whether a polyphenol-rich diet can slow the progression of or reverse HF in humans is not known. To date, in vitro and in vivo studies have reported on the protective role of polyphenols in HF. In this review, we will discuss the major mechanisms by which polyphenols mitigate HF in vitro and in vivo, including (1) reduced cardiac inflammation and oxidative stress, (2) reduced mitochondrial dysfunction, (3) improved Ca²⁺ homeostasis, (4) increased survival signaling, and (5) increased sirtuin 1 activity.

SUBMITTER: Najjar RS

PROVIDER: S-EPMC7914665 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Protective Role of Polyphenols in Heart Failure: Molecular Targets and Cellular Mechanisms Underlying Their Therapeutic Potential.

Najjar Rami S RS Feresin Rafaela G RG

International journal of molecular sciences 20210207 4

Heart failure (HF) is a leading cause of death in the United States, with a 5-year mortality rate of 50% despite modern pharmacological therapies. Plant-based diets are comprised of a diverse polyphenol profile, which lends to their association with reduced cardiovascular disease risk. Whether a polyphenol-rich diet can slow the progression of or reverse HF in humans is not known. To date, in vitro and in vivo studies have reported on the protective role of polyphenols in HF. In this review, we ...[more]

PMID: 33562294

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Project description:BackgroundHeart failure represents the terminal stage of various cardiovascular diseases. This study aims to explore the pharmacological mechanisms underlying the protective effect of Ginsenoside Rg3 against heart failure.MethodsPotential targets of Ginsenoside Rg3 were identified using SwissTargetPrediction and the Comparative Toxicogenomics Database, while heart failure-related genes were retrieved from the Comparative Toxicogenomics Database, Therapeutic Target Database, DisGeNET, and PharmGKB. Overlapping of Ginsenoside Rg3 targets with heart failure-related genes identified drug-disease interaction genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the drug-disease interaction genes to elucidate their biological functions. A protein-protein interaction network was constructed using the drug-disease interaction genes, and the hub genes were identified by topological analysis. Additionally, we validate the expression of IL-6 and TNF by real-time PCR.ResultsThe intersection of Ginsenoside Rg3 targets and heart failure-related genes yielded 15 drug-disease interaction genes. Enrichment analysis highlighted the involvement of inflammation-related GO terms and KEGG pathways, such as positive regulation of interleukin-8 and -6 production, regulation of immune effector process, cytokine receptor binding, cytokine activity, adipocytokine signaling pathway, and IL-17 signaling pathway, which are implicated in the cardioprotective effect. Topological analysis revealed four hub genes: STAT3, CASP3, TNF, and IL-6. The application of Ginsenoside Rg3 significantly reversed the elevated levels of IL-6 and TNF in the isoproterenol-treated H9c2 cell line.ConclusionsOur findings suggest that the cardioprotective effect of Ginsenoside Rg3 may be mediated through its anti-inflammation properties. Further research is required to elucidate and validate the detailed cardioprotective mechanisms of Ginsenoside Rg3.

Dataset Information

Protective Role of Polyphenols in Heart Failure: Molecular Targets and Cellular Mechanisms Underlying Their Therapeutic Potential.

Publications

Protective Role of Polyphenols in Heart Failure: Molecular Targets and Cellular Mechanisms Underlying Their Therapeutic Potential.

Similar Datasets

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