Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy
| Autor: | Leah E. Burnett, Tong Zhou, Musheng Li, Yiqui Shen, Bradley S. Ferguson, Justine S. Habibian, Abigail Bender, Levi W. Evans |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cardiotonic Agents
baicalein Phytochemicals Pharmaceutical Science Cardiomegaly phytochemical Pharmacology Biology Article emodin Analytical Chemistry lcsh:QD241-441 Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine lcsh:Organic chemistry nutrient-gene expression Drug Discovery Animals Myocytes Cardiac Physical and Theoretical Chemistry Protein kinase A Cells Cultured 030304 developmental biology apigenin Regulation of gene expression 0303 health sciences Kinase Organic Chemistry berberine hydrochloride Rats Baicalein chemistry Phytochemical Chemistry (miscellaneous) 030220 oncology & carcinogenesis Apigenin pathological cardiac hypertrophy Molecular Medicine Emodin Luteolin |
| Zdroj: | Molecules Molecules, Vol 26, Iss 1210, p 1210 (2021) Volume 26 Issue 5 |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules26051210 |
| Popis: | Plant-based foods, like fruits, vegetables, whole grains, legumes, nuts, seeds and other foodstuffs, have been deemed as heart healthy. The chemicals within these plant-based foods, i.e., phytochemicals, are credited with protecting the heart. However, the mechanistic actions of phytochemicals, which prevent clinical endpoints, such as pathological cardiac hypertrophy, are still being elucidated. We sought to characterize the overlapping and divergent mechanisms by which 18 selected phytochemicals prevent phenylephrine- and phorbol 12-myristate 13-acetate-mediated cardiomyocyte enlargement. Of the tested 18 compounds, six attenuated PE- and PMA-mediated enlargement of neonatal rat ventricular myocytes. Cell viability assays showed that apigenin, baicalein, berberine hydrochloride, emodin, luteolin and quercetin dihydrate did not reduce cell size through cytotoxicity. Four of the six phytochemicals, apigenin, baicalein, berberine hydrochloride and emodin, robustly inhibited stress-induced hypertrophy and were analyzed further against intracellular signaling and genome-wide changes in mRNA expression. The four phytochemicals differentially regulated mitogen-activated protein kinases and protein kinase D. RNA-sequencing further showed divergence in gene regulation, while pathway analysis demonstrated overlap in the regulation of inflammatory pathways. Combined, this study provided a comprehensive analysis of cardioprotective phytochemicals. These data highlight two defining observations: (1) that these compounds predominantly target divergent gene pathways within cardiac myocytes and (2) that regulation of overlapping signaling and gene pathways may be of particular importance for the anti-hypertrophic actions of these phytochemicals. Despite these new findings, future works investigating rodent models of heart failure are still needed to understand the roles for these compounds in the heart. |
| Databáze: | OpenAIRE |
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