{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T21:15:58Z","timestamp":1792444558969,"version":"4.5.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Acute myocardial infarction (MI) is a leading global cause of morbidity and mortality, where inflammatory response and programmed cell death (PCD) are critical in disease progression. \u03b2-sitosterol (\u03b2-SITO), a phytosterol with known cardioprotective effects, has been implicated in cardiovascular diseases, but its specific role and mechanisms in MI remain underexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study employed both\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      models. Male C57BL\/6J mice with MI were used to evaluate the effects of \u03b2-SITO treatment. Cardiac function was assessed via echocardiography, infarct size and fibrosis were analyzed histologically.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , cardiomyocyte viability under hypoxia and TGF-\u03b2-induced cardiac fibroblast activation were examined. Mechanistic insights were gained through transcriptomic profiling, molecular docking studies, and validation by Western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      \u03b2-SITO treatment significantly reduced myocardial infarct size, alleviated cardiac fibrosis, and improved cardiac function in MI mice.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , it enhanced cardiomyocyte viability under hypoxia and inhibited TGF-\u03b2-induced fibroblast activation. Transcriptomic analysis revealed that \u03b2-SITO modulated pathways related to immune-inflammatory responses, NF-\u03baB, and necroptosis signaling. Molecular docking confirmed its strong binding affinity to key components of these pathways. Western blotting validated the inhibition of NF-\u03baB activation and necroptosis in both hypoxic cardiomyocytes and MI mouse heart tissue.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\u03b2-SITO demonstrates significant therapeutic potential for improving post-MI recovery. Its cardioprotective effects are likely mediated through the modulation of NF-\u03baB and necroptosis signaling pathways, highlighting it as a promising candidate for MI treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1719074","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T06:33:38Z","timestamp":1767681218000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["\u03b2-sitosterol ameliorates myocardial infarction injury via modulating the NF-\u03baB and necroptosis signaling pathways"],"prefix":"10.3389","volume":"16","author":[{"given":"Jia-jia","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long-zhen","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-yan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-xin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong-gui","family":"Shan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"8870","DOI":"10.1002\/fsn3.4380","article-title":"beta-Sitosterol-Dietary sources and role in cancer and diabetes management","volume":"12","author":"Adhimoolam","year":"2024","journal-title":"Food Sci. 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