{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T16:02:26Z","timestamp":1792252946462,"version":"4.4.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"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. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Astragaloside IV (AsIV) has been reported to alleviate diabetes-induced endothelial dysfunction by inhibiting calpain-1. This study aimed to determine whether the same mechanism underlies its protective effect against diabetic cardiomyopathy (DCM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      At the\n                      <jats:italic>in vivo<\/jats:italic>\n                      level, calpain-1 knockout mice with the genotype Capn1 EK684\u2212\/\u2212 (Capn1 EK684 knockout mice) were used to establish a type 2 diabetic cardiomyopathy model. At the\n                      <jats:italic>in vitro<\/jats:italic>\n                      level, H9c2 cells and cardiac fibroblasts were stimulated with high glucose to construct corresponding models. Meanwhile, a calpain-1 overexpression lentivirus was constructed to assess the effect of calpain-1 on myocardial cell injury. Different doses of AsIV were then used to intervene in diabetic mice and H9c2 cells. Body weight, blood glucose, myocardial hypertrophy, myocardial fibrosis, cardiac function, Ca\n                      <jats:sup>2+<\/jats:sup>\n                      overload and its regulation, myocardial cell apoptosis and oxidative stress were evaluated in the current study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AsIV could not completely normalize blood glucose in mice, but could significantly improve cardiac systolic and diastolic function, myocardial hypertrophy and fibrosis. The beneficial effect of calpain-1 gene knockout on diabetic cardiomyopathy was similar to that of AsIV, and calpain-1 knockout did not further enhance the beneficial effect of AsIV. Calpain-1 overexpression abolished the beneficial effect of AsIV on high glucose induced H9c2 cell injury and fibroblast proliferation. In addition, the intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      overload, abnormal levels of sarco\/endoplasmic reticulum Ca\n                      <jats:sup>2+<\/jats:sup>\n                      -ATPase 2a (SERCA2a), phosphorylation of phospholamban (p-PLN) and ryanodine receptor 2 (p-RyR2), apoptosis and oxidative stress associated with DCM were also improved by AsIV or calpain-1 knockout, and AsIV has the capacity to suppress the overactivation of calpain-1 and calcium\/calmodulin-dependent protein kinase \u2161 (CaMKII).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      AsIV could ameliorate intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      overload, apoptosis, and oxidative stress by regulating the calpain-1\/CaMKII pathway, thereby improving myocardial hypertrophy and fibrosis caused by diabetes mellitus.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1670472","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T07:02:42Z","timestamp":1770274962000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Astragaloside IV prevents calpain-1-mediated cardiac hypertrophy and fibrosis induced by diabetes"],"prefix":"10.3389","volume":"13","author":[{"given":"Qinglong","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology , Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Second Hospital of Tianjin Medical University, Tianjin Institute of Cardiology","place":["Tianjin, China"]},{"name":"Internal Medicine-Cardiovascular Department, The First Affliated Hospital of Jinzhou Medical University","place":["Jinzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Basic Medical College, Jinzhou Medical University","place":["Jinzhou, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silin","family":"Wei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University","place":["Jinzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meili","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University","place":["Jinzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangyin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology , Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Second Hospital of Tianjin Medical University, Tianjin Institute of Cardiology","place":["Tianjin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1186\/s12916-023-02887-7","article-title":"Adipsin alleviates cardiac microvascular injury in diabetic cardiomyopathy through Csk-dependent signaling mechanism","volume":"21","author":"Zhang","year":"2023","journal-title":"Bmc Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1002\/ejhf.3347","article-title":"Diabetic myocardial disorder. 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