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Wenxin Granules, as a multi\u2010component and multi\u2010target drug, exert therapeutic effects on AF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted electrophysiological studies in ibrutinib\u2010treated mice models to assess AF inducibility and the therapeutic efficacy of Wenxin Granules. Through network pharmacology screening, we identified potential molecular targets of Wenxin Granules. Subsequent proteomic analysis revealed specific targets through which Wenxin Granules may prevent ibrutinib\u2010associated AF. These targets were further validated in mice model experiments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our study demonstrates that Wenxin Granules treatment in mice significantly reduces AF inducibility, shortens AF duration, and attenuates pathological cardiac remodeling, including left atrial (LA) enlargement and myocardial fibrosis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Through comprehensive analysis integrating proteomics with network pharmacology\u2010predicted molecular targets, we systematically screened and identified 25 core therapeutic targets of Wenxin Granules, which are primarily associated with oxidative stress and calcium protein\u2010related signaling pathways. The ibrutinib treatment group demonstrated significantly elevated expression of reactive oxygen species (ROS)\u2010related proteins, including NOX2, NOX4, p22\u2010phox, and XO. Additionally, ibrutinib substantially increased the expression of ox\u2010CaMKII, p\u2010CaMKII (Thr\u2010286), and p\u2010RyR2 (Ser2814), resulting in enhanced abnormal sarcoplasmic reticulum (SR) Ca\n                      <jats:sup>2+<\/jats:sup>\n                      release, altered mitochondrial structures, and atrial fibrosis. Notably, Wenxin Granules administration reduced the expression of these proteins (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings demonstrate that Wenxin Granules can ameliorate the occurrence and progression of AF induced by ibrutinib treatment, thereby laying the groundwork for further research and potential clinical applications in AF therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cph4.70154","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:15:32Z","timestamp":1777421732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Wenxin Granules Prevent Ibrutinib\u2010Associated Atrial Fibrillation Through Restoring Redox Balance and Calcium Homeostasis"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1441-1553","authenticated-orcid":false,"given":"Xinyu","family":"Yang","sequence":"first","affiliation":[{"name":"Dongfang Hospital Beijing University of Chinese Medicine  Beijing China"},{"name":"Cardiovascular Research Center Massachusetts General Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7794-2539","authenticated-orcid":false,"given":"Na","family":"An","sequence":"additional","affiliation":[{"name":"Key Laboratory of Chinese Internal Medicine of the Ministry of Education Dongzhimen Hospital Affiliated With Beijing University of Chinese Medicine  Beijing 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