Chrysanthemum Morifolium Extract Prevents the Development of Doxorubicin-induced Heart Failure

Objectives: Doxorubicin, an anthracycline anticancer drug, induces a cumulative and dose-dependent cardiotoxicity.Recently, Chrysanthemum morifolium extract (CME), produced from the purple chrysanthemum flower, has been reported to possess various physiological activities, such as antioxidant and anti-inflammatory effects.However, it is unknown whether CME prevents doxorubicin-induced cardiotoxicity.The aim of this study is to investigate the effectiveness of CME against doxorubicininduced cardiotoxicity.Materials and methods: H9C2 cardiomyocytes were treated with CME for 2 hours, and then stimulated with 1 µM doxorubicin.After 24 hours incubation, surviving cells were evaluated by MTT assay.Cellular apoptosis markers were assessed by western blotting.Next, to investigate the effect of CME on doxorubicin-induced cardiomyopathy in vivo, C57BL6 mice were orally administered with CME (400 mg/kg/day) or vehicle daily for 2 days before being treated with doxorubicin (20 mg/kg) intraperitoneally once.At 7 days after doxorubicin injection, an echocardiographic analysis and a TUNEL assay were performed.Results: Administering 1 mg/ml CME significantly reduced doxorubicininduced cytotoxicity in H9C2 cells.Western blotting showed that CME suppressed doxorubicin-induced increases in four markers of apoptosis: p53, phosphorylated p53, and cleaved caspase-9 and -3.The survival ratio of the CME-treated group was significantly higher than that of the vehicle-treated group in vivo.CME significantly improved doxorubicininduced left ventricular systolic dysfunction and suppressed doxorubicininduced apoptosis in mice. Conclusion:This study indicates that CME treatment reduces doxorubicininduced cardiotoxicity by suppressing apoptosis.Further studies are expected to apply CME in clinical settings for the prevention of doxorubicininduced heart failure.