Tangeretin, an active flavonoid in citrus peel, alleviates cisplatin-induced cardiotoxicity via the activation of AMPK and the prevention on mitochondrial dysfunction.

[Display omitted] • This article is the first to describe the protective effect of TG on cisplatin-induced cardiotoxicity injury in vitro and in vivo. • This study is the first to explore the protective effect of TG treatment contributed to protecting cells against cisplatin-induced apoptosis by AMPK phosphorylation and controlling mitochondria stability both in structure and function. • This study clarifies that TG treatment significantly increased the activation of AMP-activated protein kinase (AMPK) and reduced the inactivation of ACC protein and the phosphorylated p38 MAPK protein expressions which inhibited the opening of myocardial mitochondrial permeability transition pore and cell apoptosis. Cardiotoxicity is a common side effect of cisplatin in cancer treatment, often complicating patient care. Tangeretin (TG), a natural compound found in citrus peel, shows promise in protecting against cisplatin-induced heart damage. Our study investigated TG's protective effects both in cell culture and in animal models. TG effectively countered cisplatin-induced damage in heart cells, promoting mitochondrial health and glucose transporter expression. In animal studies, TG reduced markers of heart damage and improved cardiac function. Mechanistically, TG activated AMPK, reduced the inactivation of Acetyl-CoA Carboxylase (ACC) protein and inhibited p38 MAPK and prevented mitochondrial dysfunction and cell death. This research sheds light on TG's potential in safeguarding the heart from cisplatin-induced harm. [ABSTRACT FROM AUTHOR]