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Article

Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy

1
Department of Nutrition, University of Nevada, Reno, NV 89557, USA
2
Environmental Sciences Program, University of Nevada, Reno, NV 89557, USA
3
Department of Pharmacology and Physiology, University of Nevada, Reno, NV 89557, USA
4
Cellular and Molecular Biology, University of Nevada, Reno, NV 89557, USA
5
Center of Biomedical Research Excellence for Molecular and Cellular Signal Transduction in the Cardiovascular System, University of Nevada, Reno, NV 89557, USA
*
Author to whom correspondence should be addressed.
Current address: Obesity and Metabolic Unit, USDA-ARS, WHNRC, Davis, CA 95616, USA.
Academic Editors: Raluca Maria Pop, Ada Popolo and Stefan Cristian Vesa
Molecules 2021, 26(5), 1210; https://doi.org/10.3390/molecules26051210
Received: 3 February 2021 / Revised: 18 February 2021 / Accepted: 19 February 2021 / Published: 24 February 2021
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. View Full-Text
Keywords: phytochemical; emodin; berberine hydrochloride; apigenin; baicalein; pathological cardiac hypertrophy; nutrient-gene expression phytochemical; emodin; berberine hydrochloride; apigenin; baicalein; pathological cardiac hypertrophy; nutrient-gene expression
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MDPI and ACS Style

Evans, L.; Shen, Y.; Bender, A.; Burnett, L.E.; Li, M.; Habibian, J.S.; Zhou, T.; Ferguson, B.S. Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy. Molecules 2021, 26, 1210. https://doi.org/10.3390/molecules26051210

AMA Style

Evans L, Shen Y, Bender A, Burnett LE, Li M, Habibian JS, Zhou T, Ferguson BS. Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy. Molecules. 2021; 26(5):1210. https://doi.org/10.3390/molecules26051210

Chicago/Turabian Style

Evans, Levi, Yiqui Shen, Abigail Bender, Leah E. Burnett, Musheng Li, Justine S. Habibian, Tong Zhou, and Bradley S. Ferguson. 2021. "Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy" Molecules 26, no. 5: 1210. https://doi.org/10.3390/molecules26051210

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