{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:06:26Z","timestamp":1784797586199,"version":"3.55.0"},"reference-count":66,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":203,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Sepsis\u2010induced cardiac dysfunction is a major cause of high mortality in critically ill patients. Yangxin Tongluo decoction (YXTLD), a traditional Chinese medicine (TCM) formula, is clinically used for such conditions, but its therapeutic effects and underlying mechanisms remain unclear. This study investigated the protective role of YXTLD against sepsis\u2010associated cardiac dysfunction and its relationship with the Nrf2 signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An in vivo model of sepsis was established in male C57BL\/6 mice via intraperitoneal lipopolysaccharide (LPS) injection. Cardiac function was assessed by echocardiography and serum biomarkers (creatine kinase [CK], lactate dehydrogenase [LDH]). In vitro, LPS\u2010stimulated H9c2 cardiomyocytes were treated with various doses of YXTLD. Cell viability, inflammation (interleukin [IL]\u20101\u03b2, IL\u20106, TNF\u2010\u03b1), oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], catalase [CAT], glutathione [GSH]), and apoptosis were evaluated. The involvement of the Nrf2 pathway was examined using western blotting. In vivo dosage: YXTLD was administered intraperitoneally five times prior to LPS induction and continued after induction (total of seven doses over 48\u2009h). In vitro concentrations: low (50 \u03bcg\/mL), medium (100 \u03bcg\/mL), and high (150 \u03bcg\/mL) YXTLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      YXTLD significantly improved cardiac function and alleviated myocardial injury in septic mice, as evidenced by increased ejection fraction (EF; 97.87%\u2009\u00b1\u20091.20% vs. 79.05%\u2009\u00b1\u20093.04%) and fractional shortening (FS; 74.99%\u2009\u00b1\u20095.58% vs. 41.98%\u2009\u00b1\u20092.72%), together with reduced serum CK (188.60\u2009\u00b1\u200981.16 vs. 566.75\u2009\u00b1\u2009186.24\u2009U\/L) and LDH (179.70\u2009\u00b1\u200954.47 vs. 463.65\u2009\u00b1\u2009197.58\u2009U\/L) levels compared with the LPS group (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009 &lt; 0.05). In LPS\u2010stimulated H9c2 cells, YXTLD dose\u2010dependently enhanced cell viability, suppressed the expression of pro\u2010inflammatory cytokines (IL\u20106, IL\u20101\u03b2, and TNF\u2010\u03b1), reduced ROS production and lipid peroxidation, restored antioxidant capacity, and inhibited apoptosis. At 50\u2009\u03bcg\/mL, YXTLD markedly decreased IL\u20106, IL\u20101\u03b2, and TNF\u2010\u03b1 levels by ~78%, 63%, and 92%, respectively (all\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05). ROS and apoptotic cell proportions were progressively reduced with increasing YXTLD concentrations, reaching reductions of ~82% and 95%, respectively, at 150\u2009\u03bcg\/mL (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). Mechanistically, YXTLD activated the Nrf2 signaling pathway by promoting nuclear Nrf2 translocation and upregulating its downstream antioxidant proteins, including heme oxygenase\u20101 (HO\u20101), NAD(P)H quinone dehydrogenase 1 (NQO1), and glutamate\u2010cysteine ligase modifier (GCLM). YXTLD also restored CAT and GSH levels while reducing MDA accumulation, indicating attenuation of oxidative stress.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>YXTLD protects against sepsis\u2010induced cardiac dysfunction by attenuating inflammation, oxidative stress, and apoptosis through activation of the Nrf2 signaling pathway. These findings provide a pharmacological basis for YXTLD as a potential therapeutic strategy for sepsis\u2010associated cardiac dysfunction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/mi\/2804249","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T08:46:17Z","timestamp":1784796377000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Yangxin Tongluo Decoction Protects Against Sepsis\u2010Associated Cardiac Dysfunction Through Regulating Nrf2 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