{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:04Z","timestamp":1785437944807,"version":"3.56.0"},"reference-count":67,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Oxidative stress plays a pivotal role in the pathogenesis of heart failure and is closely linked to myocardial remodeling, which includes myocardial hypertrophy and fibrosis. Chrysin (CHR) has multiple medicinal effects such as antioxidant, anti\u2010inflammatory, and anti\u2010apoptosis. This research seeks to investigate whether CHR can protect against pressure overload\u2013induced myocardial remodeling and to explore the underlying mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transverse aortic constriction (TAC) surgery was conducted to establish a model of cardiac hypertrophy on male C57BL\/6J mice. A model of cardiomyocyte hypertrophy in H9C2 cells induced by angiotensin II (Ang II) was also established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results showed that CHR significantly improved survival and cardiac function, reduced myocardial hypertrophy and fibrosis, inhibited the expression of inflammatory mediators TNF\u2010\u03b1 and IL\u20101\u03b2, suppressed cell apoptosis rate, downregulated the levels of Bcl\u20102 Associated X protein (BAX) and Cleaved\u2010Caspase\u20103, and upregulated B\u2010cell lymphoma\/leukemia 2 (BCL\u20102) expression in TAC surgical mice or Ang II\u2010treated H9C2 cells. CHR could also upregulate the levels of antioxidant enzymes SOD1 and HO\u20101 by mediating the nuclear translocation and expression of NRF2 to counteract oxidative stress response. The further mechanism investigation utilizing bioinformatics analysis and western blot revealed that the disease of heart failure is associated with the phosphatidylinositol\u20113\u2011kinase (PI3K)\/serine\/threonine\u2010protein kinase B (AKT) signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, our findings demonstrated that CHR might exert the improvement effects on pressure overload\u2013induced myocardial remodeling with hypertrophy and fibrosis through regulating the PI3K\/AKT\/NRF2 pathway\u2013mediated oxidative stress response to alleviate myocardial cell inflammation and apoptosis, suggesting that CHR may be a promising therapeutic agent for cardiac diseases induced by pressure overload.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70230","type":"journal-article","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:22:32Z","timestamp":1781324552000},"page":"1373-1394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chrysin alleviates pressure overload\u2013induced myocardial remodeling through regulating the\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    \/\n                    <scp>NRF2<\/scp>\n                    pathway\u2013mediated oxidative stress response"],"prefix":"10.1002","volume":"9","author":[{"given":"Yijia","family":"Wang","sequence":"first","affiliation":[{"name":"Basic Medical Research Center The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Feng","sequence":"additional","affiliation":[{"name":"Basic Medical Research Center The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Basic Medical Research Center The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchong","family":"Fu","sequence":"additional","affiliation":[{"name":"Basic Medical Research Center The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Basic Medical Research Center The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of Techniques and Instruments for Diagnosis and Treatment of Congenital Heart Disease, Institute of Developmental and Regenerative Medicine, Xin Hua Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiping","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of General Surgery The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianpin","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhejiang\u2010Ireland Joint Laboratory for Precision Diagnosis and Treatment of Valvular Heart Diseases The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Department of Cardiology The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3483-2115","authenticated-orcid":false,"given":"Xiaoling","family":"Guo","sequence":"additional","affiliation":[{"name":"Basic Medical Research Center The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Zhejiang\u2010Ireland Joint Laboratory for Precision Diagnosis and Treatment of Valvular Heart Diseases The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Department of Cardiology The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001583"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq308"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jhh.1001707"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/2047487319901063"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2021.09.001"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.156849"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5577875"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.311148"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2017.04.012"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/01913123.2022.2163016"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112271"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2223-0"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2016.02.011"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.06.003"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2017.09.016"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116797"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2019.104496"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000989"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.156054"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26150"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.054827"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(92)90066-M"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2025.111445"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-022-02377-3"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114534"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.14165"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvac039"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad184"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109249"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104541"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0098047"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2022.2040543"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.124.323659"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0735-1097(99)00630-0"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.06.001"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.315216"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-020-09960-w"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.10.081"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.109.883652"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2017.10.014"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00646-w"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1080\/03639045.2021.1988092"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.31083\/FBL26857"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.22947"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-014-9457-4"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21968"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X15500561"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/1824-7288-38-41"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107281"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.1456"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-023-01168-6"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hfc.2005.03.007"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00820"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400476"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-023-01360-4"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-0954-x"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01853-x"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2018.08.023"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28541"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202237"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-020-10083-8"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2017.11.009"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.10.015"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.10.090"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3534"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers2020483"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116413"}],"container-title":["Animal Models and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.70230","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ame2.70230","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ame2.70230","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:16:39Z","timestamp":1785435399000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ame2.70230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,12]]},"references-count":67,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/ame2.70230"],"URL":"https:\/\/doi.org\/10.1002\/ame2.70230","archive":["Portico"],"relation":{},"ISSN":["2576-2095","2576-2095"],"issn-type":[{"value":"2576-2095","type":"print"},{"value":"2576-2095","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,12]]},"assertion":[{"value":"2026-01-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}