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However, therapeutic strategies for inhibiting ECM deposition and excessive fibrosis have still not been elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Single-nucleus RNA sequencing (snRNA-seq) revealed that the overexpression of type VI collagen-\u03b1 3 (Col6a3) in fibroblasts in the myocardial infarction area strongly promotes the process of myocardial fibrosis. Consistent results were not observed in the infarcted myocardial tissues of mice treated with 4,8-dicarboxyl-8,9-iridoid-1-glycoside (BIG). Echocardiography confirmed that BIG alleviated cardiac dysfunction in mice after myocardial I\/RI, TTC and Evans blue double staining revealed that BIG reduced the myocardial infarction size and area at risk. BIG inhibited inflammatory responses, apoptosis, and matrix metalloproteinase (MMP) secretion both in vivo and in vitro. Immunofluorescence staining revealed that BIG downregulated the expressions of TGF\u2012\u03b2 and Col6a3 in cardiac fibroblasts but not in cardiomyocytes. The PI3K-specific inhibitor LY294002 and AKT inhibitor were utilitzed to confirm that BIG suppressed myocardial fibrosis and alleviated cardiac dysfunction by activating the PI3K\/AKT pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The results provide valuable information for the treatment of myocardial fibrosis induced by myocardial I\/RI and highlight the therapeutic potential of BIG in reducing collagen deposition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15593258261444840","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T10:10:51Z","timestamp":1776507051000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["4,8-Dicarboxyl-8,9-Iridoid-1-Glycoside Alleviates Cardiac Dysfunction After Myocardial Ischaemia-Reperfusion Injury by Activating the PI3K\/AKT Pathway"],"prefix":"10.1177","volume":"24","author":[{"given":"AiJiao","family":"Sun","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of AnHui Medical University"},{"name":"Anqing Medical College Clinical Research Center (Anqing Municipal Hospital)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"CuiYu","family":"Yu","sequence":"additional","affiliation":[{"name":"Anqing Medical College Clinical Research Center (Anqing Municipal Hospital)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"FeiYan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Anqing Medical College Clinical Research Center (Anqing Municipal Hospital)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Chen","sequence":"additional","affiliation":[{"name":"Anqing Medical College Clinical Research Center (Anqing Municipal Hospital)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LiangChuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Anqing Medical College Clinical Research Center (Anqing Municipal Hospital)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ZePing","family":"Hu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of AnHui Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6059-7916","authenticated-orcid":false,"given":"WeiBing","family":"Wang","sequence":"additional","affiliation":[{"name":"Anqing Medical College Clinical Research Center (Anqing Municipal Hospital)"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,4,18]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-0403-y"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000659"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2019.02.006"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-016-0809-6"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.316958"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12265-012-9398-z"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.03.021"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz553"},{"key":"e_1_3_6_10_2","first-page":"273","article-title":"Injection of ROS-Responsive Hydrogel Loaded with IL-1\u03b2-targeted nanobody for ameliorating myocardial infarction","volume":"46","author":"Wang L","year":"2024","unstructured":"Wang L, Yu C, You T, et al. 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