{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:31:43Z","timestamp":1792787503150,"version":"4.5.0"},"reference-count":49,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"publisher","award":["81270301"],"award-info":[{"award-number":["81270301"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China (NSFC)","doi-asserted-by":"publisher","award":["81470412"],"award-info":[{"award-number":["81470412"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"1226 Major Project","award":["AWS16J018"],"award-info":[{"award-number":["AWS16J018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2018,10,1]]},"abstract":"<jats:p>\n                    Diabetic cardiac fibrosis increases ventricular stiffness and facilitates the occurrence of diastolic dysfunction. Our previous studies have shown that berberine, a natural alkaloid, attenuates cardiac ischemia-reperfusion injury in diabetic rats. The aim of present study was to investigate the effects of long-term berberine treatment on cardiac remodeling in diabetic rats and the underlying mechanisms. Diabetic rats induced by low-dose streptozotocin injection combined with 8 wk of high-fat diet displayed significant cardiac matrix collagen deposition and dysfunction, whereas berberine administration (200 mg\u00b7kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7day\n                    <jats:sup>\u22121<\/jats:sup>\n                    , gavage 4 wk) significantly ameliorated cardiac fibrosis and dysfunction and reduced cardiac IGF-1 receptor (IGF-1R) expression in diabetic rats. Interestingly, IGF-1R expression was upregulated in cardiac fibroblasts isolated from diabetic hearts or cultured in high-glucose conditions (30 mM). High glucose treatment or IGF-1R overexpression increased matrix metalloproteinase (MMP)-2\/MMP-9 expression, \u03b1-smooth muscle actin (\u03b1-SMA), and collagen type I expression in cardiac fibroblasts. In contrast, berberine treatment significantly inhibited IGF-1R expression and exerted an antifibrotic effect in high glucose-cultured cardiac fibroblasts, as manifested by decreased MMP-2\/MMP-9, \u03b1-SMA, and collagen type I expression, whereas IGF-1R siRNA plus berberine treatment did not further enhance this antifibrotic effect compared with berberine treatment alone. Taken together, long-term berberine treatment ameliorates cardiac fibrosis and dysfunction by downregulating IGF-1R expression in cardiac fibroblasts and subsequently reducing MMP-2\/MMP-9, \u03b1-SMA, and collagen type I expression in diabetic hearts. The findings suggest the therapeutic potential of berberine for diabetic cardiomyopathy associated with cardiac fibrosis.\n                  <\/jats:p>\n                  <jats:p>NEW &amp; NOTEWORTHY Berberine downregulated IGF-1 receptor expression and matrix metalloproteinase-2\/matrix metalloproteinase-9 levels in cardiac fibroblasts and thus inhibited fibroblast differentiation and collagen overproduction in diabetic hearts, suggesting a novel mechanism for antifibrotic cardioprotection of berberine in type 2 diabetes.<\/jats:p>","DOI":"10.1152\/ajpheart.00093.2018","type":"journal-article","created":{"date-parts":[[2018,6,29]],"date-time":"2018-06-29T09:42:02Z","timestamp":1530265322000},"page":"H802-H813","source":"Crossref","is-referenced-by-count":64,"title":["Antifibrotic cardioprotection of berberine via downregulating myocardial IGF-1 receptor-regulated MMP-2\/MMP-9 expression in diabetic rats"],"prefix":"10.1152","volume":"315","author":[{"given":"Guohua","family":"Li","sequence":"first","affiliation":[{"name":"School of Aerospace Medicine, Fourth Military Medical University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Xing","sequence":"additional","affiliation":[{"name":"School of Aerospace Medicine, Fourth Military Medical University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Aerospace Medicine, Fourth Military Medical University, Xi\u2019an, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenghao","family":"Geng","sequence":"additional","affiliation":[{"name":"School of Aerospace Medicine, Fourth Military Medical University, Xi\u2019an, 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