{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T14:27:22Z","timestamp":1788964042191,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T00:00:00Z","timestamp":1683504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Science and Technology Agency","award":["20K07070"],"award-info":[{"award-number":["20K07070"]}]},{"name":"Japan Science and Technology Agency","award":["19K16396"],"award-info":[{"award-number":["19K16396"]}]},{"name":"Japan Science and Technology Agency","award":["21K08069"],"award-info":[{"award-number":["21K08069"]}]},{"name":"Cardiovascular Research Fund","award":["20K07070"],"award-info":[{"award-number":["20K07070"]}]},{"name":"Cardiovascular Research Fund","award":["19K16396"],"award-info":[{"award-number":["19K16396"]}]},{"name":"Cardiovascular Research Fund","award":["21K08069"],"award-info":[{"award-number":["21K08069"]}]},{"name":"Japan Heart Foundation Research Grant","award":["20K07070"],"award-info":[{"award-number":["20K07070"]}]},{"name":"Japan Heart Foundation Research Grant","award":["19K16396"],"award-info":[{"award-number":["19K16396"]}]},{"name":"Japan Heart Foundation Research Grant","award":["21K08069"],"award-info":[{"award-number":["21K08069"]}]},{"name":"Nutrition and Food Science Fund of the Japan Society of Nutrition and Food Science","award":["20K07070"],"award-info":[{"award-number":["20K07070"]}]},{"name":"Nutrition and Food Science Fund of the Japan Society of Nutrition and Food Science","award":["19K16396"],"award-info":[{"award-number":["19K16396"]}]},{"name":"Nutrition and Food Science Fund of the Japan Society of Nutrition and Food Science","award":["21K08069"],"award-info":[{"award-number":["21K08069"]}]},{"name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","award":["20K07070"],"award-info":[{"award-number":["20K07070"]}]},{"name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","award":["19K16396"],"award-info":[{"award-number":["19K16396"]}]},{"name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","award":["21K08069"],"award-info":[{"award-number":["21K08069"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Hypertrophic stress-induced cardiac remodeling is a compensatory mechanism associated with cardiomyocyte hypertrophy and cardiac fibrosis. Continuation of this response eventually leads to heart failure. The histone acetyltransferase p300 plays an important role in the development of heart failure, and may be a target for heart failure therapy. The phenolic phytochemical 6-shogaol, a pungent component of raw ginger, has various bioactive effects; however, its effect on cardiovascular diseases has not been investigated. One micromolar of 6-shogaol suppressed phenylephrine (PE)-induced increases in cardiomyocyte hypertrophy in rat primary cultured cardiomyocytes. In rat primary cultured cardiac fibroblasts, 6-shogaol suppressed transforming growth factor-beta (TGF-\u03b2)-induced increases in L-proline incorporation. It also blocked PE- and TGF-\u03b2-induced increases in histone H3K9 acetylation in the same cells and in vitro. An in vitro p300-HAT assay revealed that 6-shogaol suppressed histone acetylation. The mice underwent transverse aortic constriction (TAC) surgery, and were administered 0.2 or 1 mg\/kg of 6-shogaol daily for 8 weeks. 6-shogaol prevented TAC-induced systolic dysfunction and cardiac hypertrophy in a dose-dependent manner. Furthermore, it also significantly inhibited TAC-induced increases in histone H3K9 acetylation. These results suggest that 6-shogaol may ameliorate heart failure through a variety of mechanisms, including the inhibition of p300-HAT activity.<\/jats:p>","DOI":"10.3390\/nu15092232","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T01:06:28Z","timestamp":1683594388000},"page":"2232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["6-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart Failure"],"prefix":"10.3390","volume":"15","author":[{"given":"Yuto","family":"Kawase","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4516-2308","authenticated-orcid":false,"given":"Yoichi","family":"Sunagawa","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan"},{"name":"Division of Translational Research, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan"},{"name":"Shizuoka General Hospital, Shizuoka 420-8527, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan"},{"name":"Division of Translational Research, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masafumi","family":"Funamoto","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan"},{"name":"Division of Translational Research, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan"},{"name":"Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9075-9982","authenticated-orcid":false,"given":"Toshihide","family":"Hamabe-Horiike","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan"},{"name":"Division of Translational Research, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan"},{"name":"Shizuoka General Hospital, Shizuoka 420-8527, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1755-2157","authenticated-orcid":false,"given":"Yasufumi","family":"Katanasaka","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan"},{"name":"Division of Translational Research, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan"},{"name":"Shizuoka General Hospital, Shizuoka 420-8527, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan"},{"name":"Division of Translational Research, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Hawke","sequence":"additional","affiliation":[{"name":"Laboratory of Scientific English, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7285-8351","authenticated-orcid":false,"given":"Kiyoshi","family":"Mori","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan"},{"name":"Shizuoka General Hospital, Shizuoka 420-8527, Japan"},{"name":"Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka 420-0881, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8827-3315","authenticated-orcid":false,"given":"Maki","family":"Komiyama","sequence":"additional","affiliation":[{"name":"Division of Translational Research, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan"},{"name":"Division of Translational Research, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan"},{"name":"Division of Translational Research, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan"},{"name":"Shizuoka General Hospital, Shizuoka 420-8527, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/ehf2.12005","article-title":"Heart failure: Preventing disease and death worldwide","volume":"1","author":"Ponikowski","year":"2014","journal-title":"ESC Heart Fail."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.15420\/cfr.2016:25:2","article-title":"Global Public Health Burden of Heart Failure","volume":"3","author":"Savarese","year":"2017","journal-title":"Card. Fail. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"63","DOI":"10.5152\/akd.2014.5731","article-title":"Mortality in heart failure patients","volume":"15","author":"Bajraktari","year":"2015","journal-title":"Anadolu Kardiyol. Derg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1161\/CIR.0b013e31820a55f5","article-title":"Forecasting the future of cardiovascular disease in the United States: A policy statement from the American Heart Association","volume":"123","author":"Heidenreich","year":"2011","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7573\/dic.2019-11-3","article-title":"DAPA-HF trial: Dapagliflozin evolves from a glucose-lowering agent to a therapy for heart failure","volume":"9","author":"Kaplinsky","year":"2020","journal-title":"Drugs Context"},{"key":"ref_6","first-page":"543","article-title":"Mini-Focus Issue: Cardiovascular Comorbidities the Transition from Hypertension to Heart Failure Contemporary Update","volume":"5","author":"Messerli","year":"2017","journal-title":"J. Am. Coll. Cardiol. HF"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/nrcardio.2016.163","article-title":"Neurohormonal activation in heart failure with reduced ejection fraction","volume":"14","author":"Hartupee","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S258","DOI":"10.1054\/jcaf.2002.129250","article-title":"Concentric versus eccentric remodeling","volume":"8","author":"Carabello","year":"2002","journal-title":"J. Card. Fail."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1253\/circj.CJ-16-0062","article-title":"From Left Ventricular Hypertrophy to Dysfunction and Failure","volume":"80","author":"Lazzeroni","year":"2016","journal-title":"Circ. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1161\/01.CIR.0000012943.91101.D7","article-title":"Tissue Doppler imaging differen-tiates physiological from pathological pressure-overload left ventricular hypertrophy in rats","volume":"105","author":"Derumeaux","year":"2002","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1146\/annurev.pharmtox.45.120403.095802","article-title":"THE CARDIAC FIBROBLAST: Therapeutic Target in Myocardial Remodeling and Failure","volume":"45","author":"Brown","year":"2005","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27457","DOI":"10.3390\/ijms161126040","article-title":"Protective Effects of Cardamom in Isoproterenol-Induced Myocardial Infarction in Rats","volume":"16","author":"Goyal","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1146\/annurev.nutr.23.011702.073237","article-title":"Bioactive Compounds in Nutrition and Health-Research Methodologies for Establishing Biological Function: The Antioxidant and Anti-inflammatory Effects of Flavonoids on Atherosclerosis","volume":"24","author":"Lefevre","year":"2004","journal-title":"Annu. Rev. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S0008-6363(00)00053-5","article-title":"Diet and prevention of coronary heart disease: The potential role of phytochemicals","volume":"47","author":"Visioli","year":"2000","journal-title":"Cardiovasc. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.foodchem.2012.04.145","article-title":"In vitro antioxidant and anti-inflammatory activities of 1-dehydro-[6]-gingerdione, 6-shogaol, 6-dehydroshogaol and hexahydrocurcumin","volume":"135","author":"Li","year":"2012","journal-title":"Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.ejphar.2016.06.044","article-title":"Pretreatment of 6-shogaol attenuates oxidative stress and inflammation in middle cerebral artery occlusion-induced mice","volume":"788","author":"Na","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.yexcr.2018.02.018","article-title":"6-Shogaol induces caspase-independent paraptosis in cancer cells via proteasomal inhibition","volume":"364","author":"Nedungadi","year":"2018","journal-title":"Exp. Cell Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"153744","DOI":"10.1016\/j.phymed.2021.153744","article-title":"Zerumbone prevents pressure overload-induced left ventricular systolic dysfunction by inhibiting cardiac hypertrophy and fibrosis","volume":"92","author":"Sari","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.jphs.2021.07.001","article-title":"Metformin suppresses phenylephrine-induced hypertrophic responses by inhibiting p300-HAT activity in cardiomyocytes","volume":"147","author":"Sunagawa","year":"2021","journal-title":"J. Pharmacol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7172","DOI":"10.1038\/s41598-020-64207-w","article-title":"The Synthetic Curcumin Analogue GO-Y030 Effectively Suppresses the Development of Pressure Overload-induced Heart Failure in Mice","volume":"10","author":"Shimizu","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.peptides.2012.01.020","article-title":"Angiotensin-(1\u20137) abrogates mitogen-stimulated proliferation of cardiac fibroblasts","volume":"34","author":"McCollum","year":"2012","journal-title":"Peptides"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9556","DOI":"10.1074\/jbc.M109.070458","article-title":"Cyclin-dependent kinase-9 is a component of the p300\/GATA4 complex required for phenylephrine-induced hypertrophy in cardiomyocytes","volume":"285","author":"Sunagawa","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1055\/a-1191-7970","article-title":"Cacao Bean Polyphenols Inhibit Cardiac Hypertrophy and Systolic Dysfunction in Pressure Overload-induced Heart Failure Model Mice","volume":"86","author":"Sari","year":"2020","journal-title":"Planta Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1161\/CIRCULATIONAHA.119.041019","article-title":"Protein Kinase N Promotes Stress-Induced Cardiac Dysfunction Through Phosphorylation of Myocardin-Related Transcription Factor A and Disruption of Its Interaction with Actin","volume":"140","author":"Sakaguchi","year":"2019","journal-title":"Circulation"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Funamoto, M., Sunagawa, Y., Katanasaka, Y., Shimizu, K., Miyazaki, Y., Sari, N., Shimizu, S., Mori, K., Wada, H., and Hasegawa, K. (2021). Histone Acetylation Domains Are Differentially Induced during Development of Heart Failure in Dahl Salt-Sensitive Rats. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041771"},{"key":"ref_26","first-page":"868","article-title":"The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats","volume":"118","author":"Morimoto","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1253\/circj.CJ-10-1072","article-title":"A Natural p300-Specific Histone Acetyltransferase Inhibitor, Curcumin, in Addition to Angiotensin-Converting Enzyme Inhibitor, Exerts Beneficial Effects on Left Ventricular Systolic Function After Myocardial Infarction in Rats","volume":"75","author":"Sunagawa","year":"2011","journal-title":"Circ. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1161\/01.CIR.91.1.161","article-title":"Myocardial Fibrosis and Stiffness with Hypertrophy and Heart Failure in the Spontaneously Hypertensive Rat","volume":"91","author":"Conrad","year":"1995","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1161\/CIRCULATIONAHA.105.585182","article-title":"Histone Acetyltransferase Activity of p300 Is Required for the Promotion of Left Ventricular Remodeling After Myocardial Infarction in Adult Mice In Vivo","volume":"113","author":"Miyamoto","year":"2006","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3593","DOI":"10.1128\/MCB.23.10.3593-3606.2003","article-title":"Cardiac p300 Is Involved in Myocyte Growth with Decompensated Heart Failure","volume":"23","author":"Yanazume","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1038\/s41401-020-00587-z","article-title":"6-Gingerol protects against cardiac remodeling by inhibiting the p38 mitogen-activated protein kinase pathway","volume":"42","author":"Ma","year":"2021","journal-title":"Acta Pharm. Sin."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1161\/CIRCULATIONAHA.107.760488","article-title":"Quantitative Control of Adaptive Cardiac Hypertrophy by Acetyltransferase p300","volume":"118","author":"Wei","year":"2008","journal-title":"Circulation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nature02006","article-title":"Smad-dependent and Smad-independent pathways in TGF-b family signalling","volume":"425","author":"Derynck","year":"2003","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1161\/01.RES.78.2.188","article-title":"SM22\u03b1, a Marker of Adult Smooth Muscle, Is Expressed in Multiple Myogenic Lineages During Embryogenesis","volume":"78","author":"Li","year":"1996","journal-title":"Circ. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.bbrc.2006.07.009","article-title":"Dynamic changes in chromatin acetylation and the expression of histone acetyltransferases and histone deacetylases regulate the SM22\u03b1 transcription in response to Smad3-mediated TGF\u03b21 signaling","volume":"348","author":"Qiu","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1161\/CIRCRESAHA.115.306565","article-title":"Cardiac fibrosis: The fibroblast awakens","volume":"118","author":"Travers","year":"2016","journal-title":"Circ. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1161\/01.RES.0000016504.08608.B9","article-title":"Histone acetylation and recruitment of serum responsive factor and CREB-binding protein onto SM22 promoter during SM22 gene expression","volume":"90","author":"Qiu","year":"2002","journal-title":"Circ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1002\/mnfr.200700515","article-title":"6-Shogaol suppressed lipopol-ysaccharide-induced up-expression of iNOS and COX-2 in murine macrophages","volume":"52","author":"Pan","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"113499","DOI":"10.1016\/j.fct.2022.113499","article-title":"Transcriptome and proteomics conjoint analysis reveal metastasis inhibitory effect of 6-shogaol as ferroptosis activator through the PI3K\/AKT pathway in human endometrial carcinoma in vitro and in vivo","volume":"170","author":"Ma","year":"2022","journal-title":"Food Chem. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.ijpharm.2019.02.013","article-title":"Tocophersolan stabilized lipid nanocapsules with high drug loading to improve the permeability and oral bioavailability of curcumin","volume":"560","author":"Bapat","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.ijpharm.2018.08.028","article-title":"Enhanced oral bioavailability and anti-gout activity of [6]-shogaol-loaded solid lipid nanoparticles","volume":"550","author":"Wang","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular properties that influence the oral bioavailability of drug candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.jconrel.2020.04.032","article-title":"Natural-lipid nanoparticle-based therapeutic approach to deliver 6-shogaol and its metabolites M2 and M13 to the colon to treat ulcerative colitis","volume":"323","author":"Yang","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1158\/1055-9965.EPI-07-2934","article-title":"Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthyhuman subjects","volume":"17","author":"Zick","year":"2008","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3056","DOI":"10.1038\/s41598-018-21125-2","article-title":"Pharmacokinetic-pharmacodynamic correlations in the development of ginger extract as an anticancer agent","volume":"8","author":"Mukkavilli","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Zhang, H., Wang, Q., Sun, C., Zhu, Y., Yang, Q., Wei, Q., Chen, J., Deng, W., Adu-Frimpong, M., and Yu, J. (2019). Enhanced Oral Bioavailability, Anti-Tumor Activity and Hepatoprotective Effect of 6-Shogaol Loaded in a Type of Novel Micelles of Polyethylene Glycol and Linoleic Acid Conjugate. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11030107"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101842","DOI":"10.1016\/j.jddst.2020.101842","article-title":"Improved oral bioavailability and target delivery of 6-shogaol via vitamin E TPGS-modified liposomes: Preparation, in-vitro and in-vivo characterizations","volume":"59","author":"Bao","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1038\/s41591-019-0643-8","article-title":"Sex differences in cardiometabolic disorders","volume":"25","author":"Gerdts","year":"2019","journal-title":"Nat. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1161\/CIRCRESAHA.108.190397","article-title":"Estrogen attenuates left ventricular and cardiomyocyte hypertrophy by an estrogen receptor-dependent pathway that increases calcineurin degradation","volume":"104","author":"Donaldson","year":"2009","journal-title":"Circ. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.carpath.2016.07.005","article-title":"A novel LAMP2 mutation associated with severe cardiac hypertrophy and microvascular remodeling in a female with Danon disease: A case report and literature review","volume":"25","author":"Bottillo","year":"2016","journal-title":"Cardiovasc. Pathol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1253\/circj.CJ-10-0196","article-title":"Sex and Gender Differences in Myocardial Hypertrophy and Heart Failure","volume":"74","author":"Seeland","year":"2010","journal-title":"Circ. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/embor.2012.87","article-title":"Sex and gender differences in health. Science & Society Series on Sex and Science","volume":"13","year":"2012","journal-title":"EMBO Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1038\/465690a","article-title":"Males still dominate animal studies","volume":"465","author":"Zucker","year":"2010","journal-title":"Nature"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/9\/2232\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:31:34Z","timestamp":1760124694000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/9\/2232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,8]]},"references-count":53,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["nu15092232"],"URL":"https:\/\/doi.org\/10.3390\/nu15092232","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,8]]}}}