{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:10:30Z","timestamp":1782907830313,"version":"3.54.5"},"reference-count":65,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R15 HL143496"],"award-info":[{"award-number":["R15 HL143496"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20 GM130459"],"award-info":[{"award-number":["P20 GM130459"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["OIA-1826801"],"award-info":[{"award-number":["OIA-1826801"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"publisher","award":["Hatch-NEV00727"],"award-info":[{"award-number":["Hatch-NEV00727"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"publisher","award":["Hatch-NEV00767"],"award-info":[{"award-number":["Hatch-NEV00767"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/molecules26051210","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T02:36:13Z","timestamp":1614220573000},"page":"1210","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Divergent and Overlapping Roles for Selected Phytochemicals in the Regulation of Pathological Cardiac Hypertrophy"],"prefix":"10.3390","volume":"26","author":[{"given":"Levi","family":"Evans","sequence":"first","affiliation":[{"name":"Department of Nutrition, University of Nevada, Reno, NV 89557, USA"},{"name":"Environmental Sciences Program, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqui","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Bender","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah E.","family":"Burnett","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine S.","family":"Habibian","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biology, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2361-1931","authenticated-orcid":false,"given":"Tong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0357-6075","authenticated-orcid":false,"given":"Bradley S.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of Nevada, Reno, NV 89557, USA"},{"name":"Environmental Sciences Program, University of Nevada, Reno, NV 89557, USA"},{"name":"Center of Biomedical Research Excellence for Molecular and Cellular Signal Transduction in the Cardiovascular System, University of Nevada, Reno, NV 89557, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"ref_1","first-page":"285","article-title":"Efficacy and safety of ginkgo injections in the treatment of angina pectoris caused by coronary heart disease in China: A network Meta-analysis and systematic review","volume":"39","author":"Tan","year":"2019","journal-title":"J. Tradit. Chin. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Conesa, M.T., Chambers, K., Combet, E., Pinto, P., Garcia-Aloy, M., Andr\u00e9s-Lacueva, C., Pascual-Teresa, S.D., Mena, P., Ristic, A.K., and Hollands, W.J. (2018). Meta-analysis of the effects of foods and derived products containing ellagitannins and anthocyanins on cardiometabolic biomarkers: Analysis of factors influencing variability of the individual responses. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030694"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S308","DOI":"10.1093\/advances\/nmz113","article-title":"Associations between Dietary Pulses Alone or with Other Legumes and Cardiometabolic Disease Outcomes: An Umbrella Review and Updated Systematic Review and Meta-analysis of Prospective Cohort Studies","volume":"10","author":"Viguiliouk","year":"2019","journal-title":"Adv. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1177\/2047487319843667","article-title":"Dietary components and risk of cardiovascular disease and all-cause mortality: A review of evidence from meta-analyses","volume":"26","author":"Kwok","year":"2019","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Al-Shafei, A.I.M., and El-Gendy, O.A.A. (2019). Regular consumption of green tea improves pulse pressure and induces regression of left ventricular hypertrophy in hypertensive patients. Physiol. Rep., 7.","DOI":"10.14814\/phy2.14030"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pop, R.M., Popolo, A., Trifa, A.P., and Stanciu, L.A. (2018). Phytochemicals in cardiovascular and respiratory diseases: Evidence in oxidative stress and inflammation. Oxid. Med. Cell. Longev., 1603872.","DOI":"10.1155\/2018\/1603872"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Evans, L., and Ferguson, B. (2018). Food Bioactive HDAC Inhibitors in the Epigenetic Regulation of Heart Failure. Nutrients, 10.","DOI":"10.3390\/nu10081120"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nienaber, J.J., Tachibana, H., Naga Prasad, S.V., Esposito, G., Wu, D., Mao, L., and Rockman, H.A. (2003). Inhibition of receptor-localized PI3K preserves cardiac \u03b2-adrenergic receptor function and ameliorates pressure overload heart failure. J. Clin. Invest.","DOI":"10.1172\/JCI18213"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Devereux, R.B., Wachtell, K., Gerdts, E., Boman, K., Nieminen, M.S., Papademetriou, V., Rokkedal, J., Harris, K., Aurup, P., and Dahl\u00f6f, B. (2004). Prognostic significance of left ventricular mass change during treatment of hypertension. J. Am. Med. Assoc.","DOI":"10.1016\/S0735-1097(03)81645-5"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Godoy, L.D., Lucas, J.E., Bender, A.J., Romanick, S.S., and Ferguson, B.S. (2016). Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity. Mol. Nutr. Food Res., 1600744.","DOI":"10.1002\/mnfr.201600744"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"28930","DOI":"10.1074\/jbc.M303113200","article-title":"Dose-dependent blockade to cardiomyocyte hypertrophy by histone deacetylase inhibitors","volume":"278","author":"Antos","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1161\/01.HYP.37.5.1222","article-title":"Activation of cardiac c-Jun NH2-terminal kinases and p38-mitogen-activated protein kinases with abrupt changes in hemodynamic load","volume":"37","author":"Fischer","year":"2001","journal-title":"Hypertension"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zhao, L., Cheng, G., Jin, R., Afzal, M.R., Samanta, A., Xuan, Y.T., Girgis, M., Elias, H.K., Zhu, Y., and Davani, A. (2016). Deletion of Interleukin-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Dysfunction. Circ. Res.","DOI":"10.1161\/CIRCRESAHA.116.308688"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Monovich, L., Vega, R.B., Meredith, E., Miranda, K., Rao, C., Capparelli, M., Lemon, D.D., Phan, D., Koch, K.A., and Chapo, J.A. (2010). A novel kinase inhibitor establishes a predominant role for protein kinase D as a cardiac class IIa histone deacetylase kinase. FEBS Lett.","DOI":"10.1016\/j.febslet.2009.12.014"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Evans, L.W., Bender, A., Burnett, L., Godoy, L., Shen, Y., Staten, D., Zhou, T., Angermann, J.E., and Ferguson, B.S. (2020). Emodin and emodin-rich rhubarb inhibits histone deacetylase (HDAC) activity and cardiac myocyte hypertrophy. J. Nutr. Biochem., 108339.","DOI":"10.1016\/j.jnutbio.2019.108339"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chen, H.M., Hsu, J.H., Liou, S.F., Chen, T.J., Chen, L.Y., Chiu, C.C., and Yeh, J.L. (2014). Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways. BMC Complement. Altern. Med., 14.","DOI":"10.1186\/1472-6882-14-233"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"975","DOI":"10.2147\/DDDT.S195412","article-title":"Emodin alleviates myocardial ischemia\/reperfusion injury by inhibiting gasdermin D-mediated pyroptosis in cardiomyocytes","volume":"Volume 13","author":"Ye","year":"2019","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1159\/000459708","article-title":"Baicalin Attenuates Cardiac Dysfunction and Myocardial Remodeling in a Chronic Pressure-Overload Mice Model","volume":"41","author":"Zhang","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1007\/s11418-020-01387-9","article-title":"Effects of Sanoshashinto on left ventricular hypertrophy and gut microbiota in spontaneously hypertensive rats","volume":"74","author":"Wu","year":"2020","journal-title":"J. Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1002\/jcb.24445","article-title":"Baicalein protects against cardiac hypertrophy through blocking MEK-ERK1\/2 signaling","volume":"114","author":"Zong","year":"2013","journal-title":"J. Cell. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.lfs.2015.12.036","article-title":"Cardioprotective effects of baicalein on heart failure via modulation of Ca2 + handling proteins in vivo and in vitro","volume":"145","author":"Zhao","year":"2016","journal-title":"Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1093\/ajh\/hpu194","article-title":"Baicalein attenuates angiotensin II-induced cardiac remodeling via inhibition of AKT\/mTOR, ERK1\/2, NF-\u03baB, and calcineurin signaling pathways in mice","volume":"28","author":"Wang","year":"2015","journal-title":"Am. J. Hypertens."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1142\/S0192415X14500505","article-title":"Baicalein inhibits HMGB1 release and MMP-2\/-9 expression in lipopolysaccharide-induced cardiac hypertrophy","volume":"42","author":"Chen","year":"2014","journal-title":"Am. J. Chin. Med."},{"key":"ref_24","first-page":"1874","article-title":"Dietary flavonoid aglycones and their glycosides: Which show better biological significance?","volume":"57","author":"Xiao","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1017\/jns.2016.41","article-title":"Flavonoids: An overview","volume":"5","author":"Panche","year":"2016","journal-title":"J. Nutr. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yan, L., Zhang, J.D., Wang, B., Lv, Y.J., Jiang, H., Liu, G.L., Qiao, Y., Ren, M., and Guo, X.F. (2013). Quercetin Inhibits Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats and Inhibits Angiotensin II-Induced H9C2 Cells Hypertrophy by Enhancing PPAR-\u03b3 Expression and Suppressing AP-1 Activity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072548"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1055\/s-0043-103415","article-title":"Kaempferol Attenuates Cardiac Hypertrophy via Regulation of ASK1\/MAPK Signaling Pathway and Oxidative Stress","volume":"83","author":"Feng","year":"2017","journal-title":"Planta Med."},{"key":"ref_28","first-page":"390","article-title":"Effect of apigenin, kaempferol and resveratrol on the expression of interleukin-1\u03b2 and tumor necrosis factor-\u03b1 genes in J774.2 macrophages","volume":"57","author":"Kowalski","year":"2005","journal-title":"Pharmacol. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Palacz-Wrobel, M., Borkowska, P., Paul-Samojedny, M., Kowalczyk, M., Fila-Danilow, A., Suchanek-Raif, R., and Kowalski, J. (2017). Effect of apigenin, kaempferol and resveratrol on the gene expression and protein secretion of tumor necrosis factor alpha (TNF-\u03b1) and interleukin-10 (IL-10) in RAW-264.7 macrophages. Biomed. Pharmacother.","DOI":"10.1016\/j.biopha.2017.07.054"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Caltagirone, S., Rossi, C., Poggi, A., Ranelletti, F.O., Natali, P.G., Brunetti, M., Aiello, F.B., and Piantelli, M. (2000). Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int. J. Cancer.","DOI":"10.1002\/1097-0215(20000815)87:4<595::AID-IJC21>3.0.CO;2-5"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Janssen, K., Mensink, R.P., Cox, F.J.J., Harryvan, J.L., Hovenier, R., Hollman, P.C., and Katan, M.B. (1998). Effects of the flavonoids quercetin and apigenin on hemostasis in healthy volunteers: Results from an in vitro and a dietary supplement study. Am. J. Clin. Nutr.","DOI":"10.1093\/ajcn\/67.2.255"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Cos, P., Ying, L., Calomme, M., Hu, J.P., Cimanga, K., Van Poel, B., Pieters, L., Vlietinck, A.J., and Vanden Berghe, D. (1998). Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. J. Nat. Prod.","DOI":"10.1021\/np970237h"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.bioorg.2017.08.001","article-title":"Structure-activity relationships and molecular docking of thirteen synthesized flavonoids as horseradish peroxidase inhibitors","volume":"74","author":"Mahfoudi","year":"2017","journal-title":"Bioorg. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wright, B., Watson, K.A., McGuffin, L.J., Lovegrove, J.A., and Gibbins, J.M. (2015). GRID and docking analyses reveal a molecular basis for flavonoid inhibition of Src family kinase activity. J. Nutr. Biochem.","DOI":"10.1016\/j.jnutbio.2015.05.004"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jscs.2015.11.002","article-title":"Evaluation of the biological potencies of newly synthesized berberine derivatives bearing benzothiazole moieties with substituted functionalities","volume":"21","author":"Mistry","year":"2017","journal-title":"J. Saudi Chem. Soc."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Shimmyo, Y., Kihara, T., Akaike, A., Niidome, T., and Sugimoto, H. (2008). Flavonols and flavones as BACE-1 inhibitors: Structure-activity relationship in cell-free, cell-based and in silico studies reveal novel pharmacophore features. Biochim. Biophys. Acta Gen. Subj.","DOI":"10.1016\/j.bbagen.2008.01.017"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Scafuri, B., Bontempo, P., Altucci, L., De Masi, L., and Facchiano, A. (2020). Molecular docking simulations on histone deacetylases (Hdac)-1 and-2 to investigate the flavone binding. Biomedicines, 8.","DOI":"10.3390\/biomedicines8120568"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104739","DOI":"10.1016\/j.phrs.2020.104739","article-title":"A machine learning-driven study indicates emodin improves cardiac hypertrophy by modulation of mitochondrial SIRT3 signaling","volume":"155","author":"Gao","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4643","DOI":"10.3892\/mmr.2016.5838","article-title":"Emodin suppresses silica-induced lung fibrosis by promoting Sirt1 signaling via direct contact","volume":"14","author":"Yang","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7440","DOI":"10.1073\/pnas.1221999110","article-title":"Interference with ERKThr188 phosphorylation impairs pathological but not physiological cardiac hypertrophy","volume":"110","author":"Ruppert","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Slone, S., Anthony, S.R., Wu, X., Benoit, J.B., Aube, J., Xu, L., and Tranter, M. (2016). Activation of HuR downstream of p38 MAPK promotes cardiomyocyte hypertrophy. Cell. Signal.","DOI":"10.1016\/j.cellsig.2016.08.005"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zechner, D., Thuerauf, D.J., Hanford, D.S., McDonough, P.M., and Glembotski, C.C. (1997). A role for the p38 mitogen-activated protein kinase pathway in myocardial cell growth, sarcomeric organization, and cardiac-specific gene expression. J. Cell Biol.","DOI":"10.1083\/jcb.139.1.115"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Wang, Y., Su, B., Sah, V.P., Brown, J.H., Han, J., and Chien, K.R. (1998). Cardiac hypertrophy induced by Mitogen-activated Protein Kinase Kinase 7, a specific activator for c-Jun NH2-terminal kinase in ventricular muscle cells. J. Biol. Chem.","DOI":"10.1016\/S0021-9258(19)84316-8"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liu, W., Zi, M., Jin, J., Prehar, S., Oceandy, D., Kimura, T.E., Lei, M., Neyses, L., Weston, A.H., and Cartwright, E.J. (2009). Cardiac-specific deletion of Mkk4 reveals its role in pathological hypertrophic remodeling but not in physiological cardiac growth. Circ. Res.","DOI":"10.1161\/CIRCRESAHA.108.188292"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1172\/JCI24178","article-title":"Protein kinase cascades in the regulation of cardiac hypertrophy","volume":"115","author":"Dorn","year":"2005","journal-title":"J. Clin. Invest."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Harrison, B.C., Kim, M.-S., van Rooij, E., Plato, C.F., Papst, P.J., Vega, R.B., McAnally, J.A., Richardson, J.A., Bassel-Duby, R., and Olson, E.N. (2006). Regulation of Cardiac Stress Signaling by Protein Kinase D1. Mol. Cell. Biol.","DOI":"10.1128\/MCB.26.10.3875-3888.2006"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s11883-014-0435-z","article-title":"Inflammation and cardiovascular disease: From pathogenesis to therapeutic target","volume":"16","author":"Golia","year":"2014","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis\u2014An Inflammatory Disease","volume":"340","author":"Ross","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Purcell, N.H., Tang, G., Yu, C., Mercurio, F., DiDonato, J.A., and Lin, A. (2001). Activation of NF-\u03baB is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes. Proc. Natl. Acad. Sci. USA.","DOI":"10.1073\/pnas.111155798"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1161\/HYPERTENSIONAHA.118.12267","article-title":"HIMF (Hypoxia-Induced Mitogenic Factor)-IL (Interleukin)-6 signaling mediates cardiomyocyte-fibroblast crosstalk to promote cardiac hypertrophy and fibrosis","volume":"73","author":"Kumar","year":"2019","journal-title":"Hypertension"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Lai, N.C., Gao, M.H., Tang, E., Tang, R., Guo, T., Dalton, N.D., Deng, A., and Tang, T. (2012). Pressure overload-induced cardiac remodeling and dysfunction in the absence of interleukin 6 in mice. Lab. Investig.","DOI":"10.1038\/labinvest.2012.97"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"561","DOI":"10.4049\/immunohorizons.2000075","article-title":"Extracellular miR-146a-5p Induces Cardiac Innate Immune Response and Cardiomyocyte Dysfunction","volume":"4","author":"Shimada","year":"2020","journal-title":"ImmunoHorizons"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wang, L., Zhang, Y.L., Lin, Q.Y., Liu, Y., Guan, X.M., Ma, X.L., Cao, H.J., Liu, Y., Bai, J., and Xia, Y.L. (2018). CXCL1-CXCR2 axis mediates angiotensin II-induced cardiac hypertrophy and remodelling through regulation of monocyte infiltration. Eur. Heart J.","DOI":"10.1093\/eurheartj\/ehy085"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wang, X., Li, W., Yue, Q., Du, W., Li, Y., Liu, F., Yang, L., Zhao, R., and Hu, J. (2021). C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload. Mol. Med. Rep., 23.","DOI":"10.3892\/mmr.2020.11687"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wang, M., Firrman, J., Liu, L.S., and Yam, K. (2019). A review on flavonoid apigenin: Dietary intake, ADME, antimicrobial effects, and interactions with human gut microbiota. Biomed Res. Int., 7010467.","DOI":"10.1155\/2019\/7010467"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Pang, H., Xue, W., Shi, A., Li, M., Li, Y., Cao, G., Yan, B., Dong, F., Xiao, W., and He, G. (2016). Multiple-Ascending-Dose Pharmacokinetics and Safety Evaluation of Baicalein Chewable Tablets in Healthy Chinese Volunteers. Clin. Drug Investig.","DOI":"10.1007\/s40261-016-0418-7"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Li, G., Zhao, M., Qiu, F., Sun, Y., and Zhao, L. (2019). Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: An open-label, randomized, parallel study in healthy chinese subjects. Drug Des. Devel. Ther.","DOI":"10.2147\/DDDT.S185487"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jep.2012.10.009","article-title":"Pharmacokinetics and tissue distribution of resveratrol, emodin and their metabolites after intake of Polygonum cuspidatum in rats","volume":"144","author":"Lin","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"11320","DOI":"10.1021\/acs.jafc.8b03273","article-title":"Absorption and Metabolism of Luteolin in Rats and Humans in Relation to in Vitro Anti-inflammatory Effects","volume":"66","author":"Hayasaka","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1079\/BJN20061809","article-title":"Absorption, excretion and metabolite profiling of methyl-, glucuronyl-, glucosyl- and sulpho-conjugates of quercetin in human plasma and urine after ingestion of onions","volume":"96","author":"Mullen","year":"2006","journal-title":"Br. J. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.semcancer.2007.05.003","article-title":"Interindividual differences in phytochemical metabolism and disposition","volume":"17","author":"Lampe","year":"2007","journal-title":"Semin. Cancer Biol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Gradolatto, A., Basly, J.P., Berges, R., Teyssier, C., Chagnon, M.C., Siess, M.H., and Canivenc-Lavier, M.C. (2005). Pharmacokinetics and metabolism of apigenin in female and male rats after a single oral administration. Drug Metab. Dispos.","DOI":"10.1124\/dmd.104.000893"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Shi, Y., Li, J., Ren, Y., Wang, H., Cong, Z., Wu, G., Du, L., Li, H., and Zhang, X. (2015). Pharmacokinetics and tissue distribution of emodin loaded nanoemulsion in rats. J. Drug Deliv. Sci. Technol.","DOI":"10.1016\/j.jddst.2015.10.019"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.yjmcc.2016.04.015","article-title":"Discovery of novel small molecule inhibitors of cardiac hypertrophy using high throughput, high content imaging","volume":"97","author":"Reid","year":"2016","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ferguson, B.S., Nam, H., Hopkins, R.G., and Morrison, R.F. (2010). Impact of reference gene selection for target gene normalization on experimental outcome using real- time qRT-PCR in adipocytes. 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