{"id":12174,"date":"2023-07-28T15:03:11","date_gmt":"2023-07-28T15:03:11","guid":{"rendered":"https:\/\/www.nanion.de\/?post_type=resource_library&#038;p=12174"},"modified":"2023-07-28T15:03:11","modified_gmt":"2023-07-28T15:03:11","slug":"2023-berberine-attenuates-sunitinib-induced-cardiac-dysfunction-by-normalizing-calcium-regulation-disorder-via-sgk1-activation","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/zh-hans\/resource_library\/2023-berberine-attenuates-sunitinib-induced-cardiac-dysfunction-by-normalizing-calcium-regulation-disorder-via-sgk1-activation\/","title":{"rendered":"2023 &#8211; Berberine attenuates sunitinib-induced cardiac dysfunction by normalizing calcium regulation disorder via SGK1 activation"},"content":{"rendered":"<p>Sunitinib\u00a0(SNT)-induced cardiotoxicity is associated with abnormal\u00a0calcium\u00a0regulation caused by\u00a0phosphoinositide 3 kinase\u00a0inhibition in the heart.\u00a0Berberine\u00a0(BBR) is a natural compound that exhibits cardioprotective effects and regulates\u00a0calcium\u00a0homeostasis. We hypothesized that BBR ameliorates SNT-induced cardiotoxicity by normalizing the calcium regulation disorder via serum and glucocorticoid-regulated kinase 1 (SGK1) activation. Mice, neonatal rat cardiomyocytes (NRVMs), and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to study the effects of BBR-mediated SGK1 activity on the calcium regulation disorder caused by SNT as well as the underlying mechanism. BBR offered prevention against SNT-induced cardiac\u00a0systolic dysfunction, QT interval\u00a0prolongation, and histopathological changes in mice. After the oral administration of SNT, the Ca<sup>2+<\/sup>\u00a0transient and contraction of cardiomyocytes was significantly inhibited, whereas BBR exhibited an antagonistic effect. In NRVMs, BBR was significantly preventive against the SNT-induced reduction of calcium transient amplitude,\u00a0prolongation\u00a0of calcium transient recovery, and decrease in SERCA2a protein expression; however, SGK1 inhibitors resisted the preventive effects of BBR. In hiPSC-CMs, BBR\u00a0pretreatment\u00a0significantly prevented SNT from inhibiting the contraction, whereas coincubation with SGK1 inhibitors antagonized the effects of BBR. These findings indicate that BBR attenuates SNT-induced cardiac dysfunction by normalizing the calcium regulation disorder via SGK1 activation.<\/p>\n<p>&nbsp;<\/p>\n<p>Read more in the publication <a href=\"https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S027869152300145X\">here<\/a>.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[34],"resource_type":[75],"application_areas":[53,76,77],"therapeutic_areas":[143,290],"target_categories":[],"target_families":[],"targets":[],"resource_keyword":[],"class_list":["post-12174","resource_library","type-resource_library","status-publish","hentry","products_tags-cardioexcyte-96","resource_type-publication","application_areas-assay-development-and-validation","application_areas-drug-discovery","application_areas-cell-ipscs-profiling","therapeutic_areas-assay-development-and-validation","therapeutic_areas-toxicology"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/12174","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=12174"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=12174"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=12174"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=12174"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=12174"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=12174"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=12174"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=12174"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=12174"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}