{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T02:25:36Z","timestamp":1793759136458,"version":"4.6.1"},"reference-count":48,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>Myocardial fibrosis, a critical pathogenic driver of cardiovascular events, is primarily characterized by extracellular matrix deposition and cardiac fibroblast proliferation and activation. Eriodictyol (ERIO) is an extractable natural compound widely found in fruits and vegetables, possessing positive antioxidant and anti\u2010inflammatory benefits. This study primarily explores the role and molecular mechanism of ERIO in pressure overload\u2010induced myocardial fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach<\/jats:title>\n                    <jats:p>\n                      We established an in vivo cardiac remodelling model using transverse aortic constriction (TAC) surgery and an in vitro myocardial fibrosis model induced by transforming growth factor\n                      <jats:italic>\u03b2<\/jats:italic>\n                      (TGF\u2010\n                      <jats:italic>\u03b2<\/jats:italic>\n                      ). For mechanistic exploration, we administered adeno\u2010associated virus (AAV) carrying cardiac fibroblast\u2010specific apoptosis signal\u2010regulating kinase 1 (ASK1) overexpression via tail vein injection, generated a cardiac fibroblast\u2010specific ASK1 knockout mouse model, and established an in vitro neonatal rat cardiac fibroblast (NRCF) model with co\u2010intervention of the selective ASK1 inhibitor GS\u20104977.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results<\/jats:title>\n                    <jats:p>ERIO significantly improved pressure overload\u2010induced cardiac dysfunction and myocardial fibrosis. In addition, ERIO inhibited oxidative stress and inflammatory responses and improved mitochondrial function. Specifically, our mechanistic study revealed that ERIO binds to the K398 site of ASK1, regulating its ubiquitination and phosphorylation activation, down\u2010regulating its downstream JNK\/P38 signalling axis and inhibiting the proliferation and activation of cardiac fibroblasts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and implications<\/jats:title>\n                    <jats:p>ERIO is a safe, effective natural flavonoid with promising preclinical efficacy, suggesting its potential clinical translation for myocardial fibrosis and offering new therapeutic targets to prevent heart failure progression.<\/jats:p>\n                  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