阿霉素（DOX）是一种常用的化疗药物，用于治疗血液恶性肿瘤和实体瘤；然而，其临床应用因显着的心脏毒性而受到限制。 Cynaroside (Cyn) 是一种分布在金银花中的黄酮苷，已证实在调节炎症、焦亡和氧化应激方面具有潜在的生物学功能。在此，我们在 DOX 诱导的心脏毒性 (DIC) 小鼠模型中评估了 Cyn 的作用，该模型是通过腹腔注射 DOX (5 mg/kg) 每周一次，持续三周建立的。治疗组的小鼠每两天接受右雷佐生、MCC950 和 Cyn 治疗。通过血液生化、组织病理学、免疫组织化学、逆转录定量聚合酶链反应（RT-qPCR）和蛋白质印迹来研究 Cyn 治疗的心脏保护作用和潜在机制。结果证明了 Cyn 治疗在减轻 DIC 方面的显着益处；能在一定程度上有效缓解氧化应激，维持细胞凋亡平衡，增强小鼠心功能。这些作用是通过调节焦亡相关基因的转录水平来实现的，例如核苷酸结合寡聚化结构域样受体蛋白 3 (NLRP3)、caspase-1 和gasdermin D (GSDMD)。从机制上讲，对于 DOX 诱导的心肌损伤，Cyn 可以显着调节关键基因的表达，包括单磷酸腺苷激活蛋白激酶（AMPK）、过氧化物酶体增殖物激活受体 γ 共激活剂-1α（PGC-1α）、sirtuin 3（SIRT3）和核因子红细胞 2 相关因子 2 (Nrf2)。我们将其归因于 AMPK/SIRT3/Nrf2 通路的介导，该通路在预防 DOX 诱导的心肌细胞损伤中发挥着核心作用。总之，本研究证实了 Cyn 通过调节 AMPK/SIRT3/Nrf2 通路在 DIC 中的治疗潜力。

Doxorubicin (DOX) is a commonly administered chemotherapy drug for treating hematological malignancies and solid tumors; however, its clinical application is limited by significant cardiotoxicity. Cynaroside (Cyn) is a flavonoid glycoside distributed in honeysuckle, with confirmed potential biological functions in regulating inflammation, pyroptosis, and oxidative stress. Herein, the effects of Cyn were evaluated in a DOX-induced cardiotoxicity (DIC) mouse model, which was established by intraperitoneal injections of DOX (5 mg/kg) once a week for three weeks. The mice in the treatment group received dexrazoxane, MCC950, and Cyn every two days. Blood biochemistry, histopathology, immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting were conducted to investigate the cardioprotective effects and potential mechanisms of Cyn treatment. The results demonstrated the significant benefits of Cyn treatment in mitigating DIC; it could effectively alleviate oxidative stress to a certain extent, maintain the equilibrium of cell apoptosis, and enhance the cardiac function of mice. These effects were realized via regulating the transcription levels of pyroptosis-related genes, such as nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), caspase-1, and gasdermin D (GSDMD). Mechanistically, for DOX-induced myocardial injury, Cyn could significantly modulate the expression of pivotal genes, including adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), sirtuin 3 (SIRT3), and nuclear factor erythroid 2-related factor 2 (Nrf2). We attribute it to the mediation of AMPK/SIRT3/Nrf2 pathway, which plays a central role in preventing DOX-induced cardiomyocyte injury. In conclusion, the present study confirms the therapeutic potential of Cyn in DIC by regulating the AMPK/SIRT3/Nrf2 pathway.