多柔比星（DOX）是一种可用于治疗各种肿瘤的化疗药物，然而，由于其有心脏毒性，其疗效受到限制。复叶柞蚕（Cycas thouarsii）乙酸乙酯组分中分离出一种天然双黄酮类化合物——阔叶针叶植物素（AMF），其表现出有前景的抗癌、抗炎和抗氧化作用。因此，我们的研究旨在探索AMF是否能增强对DOX心脏毒性的心脏保护作用，并揭示心脏保护的潜在机制。我们将小鼠分为四组：正常对照组，未经处理的DOX组，以及分别每天腹腔注射40和80 mg/kg AMF治疗的DOX组，在DOX给药前四天和额外三天的治疗中评估心脏毒性。超声心动图显示，AMF 80治疗组受到了DOX心脏毒性的保护。此外，它缓解了组织病理结构改变，有效地恢复了心重量和体重比例。这些效应在生化水平上得到了证实，血清肌酸激酶-MB（CK-MB）和天门冬氨酸转移酶（AST）水平显著降低。AMF通过明显减少DOX组相应的核呼吸因子-1（NRF-1）、线粒体转录因子A（TFAM）、心肌保护蛋白-27（HSP-27）表达水平，有效地恢复了这些水平。此外，AMF缓解了氧化应激条件和显著抑制了NADPH氧化酶（NOX）表达水平。它还显示出显著的抗炎作用，通过抑制白细胞介素-6（IL-6）表达和减少核因子Kabb A（NF-κb）免疫染色。此外，AMF显著减少了心脏组织中FAS配体（FASL）的表达和p53的免疫染色。这项研究是首次研究AMF对急性DOX心脏毒性的体内潜在有益作用，可能通过发挥抗氧化、抗炎和抗凋亡作用以及恢复线粒体功能实现。版权所有 © 2022 The Authors. 由Elsevier Masson SAS出版。保留所有权利。

Doxorubicin (DOX) is an available chemotherapeutic drug for treating various tumors. However, its effectiveness is limited by cardiotoxicity. Amentoflavone (AMF), a natural biflavonoid separated from Cycas thouarsii ethyl acetate fraction, displays promising anticancer, anti-inflammatory, and antioxidant effects. Thus, our research aims to explore whether AMF could boost cardioprotective effects against DOX cardiotoxicity and reveal the potential underlying mechanisms of cardioprotection. Mice were classified into four groups; Normal control, Untreated DOX group, and DOX groups treated with AMF (40 and 80 mg/kg, respectively) intraperitoneal injection daily for four days before doxorubicin administration and for additional three days following DOX administration to assess cardiotoxicity. Echocardiography showed that AMF 80 treated group was protected from DOX cardiotoxicity. Additionally, it alleviated histopathological structural alterations and effectively restored heart weight and body weight ratio. These effects were confirmed biochemically by a substantially reduced serum creatine kinase-MB (CK-MB) and aspartate aminotransferase (AST) levels. AMF effectively restored nuclear respiratory factor-1(NRF-1), mitochondrial transcription factor A (TFAM), and normalized heat shock protein - 27(HSP-27) expression levels compared to the DOX group. Moreover, AMF mitigated oxidative stress conditions and significantly suppressed NADPH oxidase (NOX) expression levels. It also showed significant anti-inflammatory effects via suppressing interleukin-6 (IL-6) expression and decreasing nuclear factor Kabba B (NF-κb) immune-staining. In addition, AMF markedly reduced FAS ligand (FASL) expression and p53 immune staining in cardiac tissue. This study is the first for the in vivo potential beneficial effects of AMF against acute DOX cardiotoxicity, possibly via exerting antioxidant, anti-inflammatory, and anti-apoptotic effects and restoring mitochondrial function.Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.