Zhou Jingquan, Liu Huan, Jiang Feng, Yu Xiyong, Wang Panxia, Wu Xiaoqian
Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, the School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, PR China.
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, CAMS Key Laboratory for Prevention and Control of Hematological Disease Treatment Related Infection, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, PR China.
Phytomedicine. 2025 Sep;145:157020. doi: 10.1016/j.phymed.2025.157020. Epub 2025 Jun 25.
Doxorubicin (DOX), a cornerstone chemotherapeutic agent, is plagued by dose-dependent cardiotoxicity that compromises its clinical utility. Despite advances in understanding DOX-induced cardiotoxicity (DIC), effective interventions remain limited. Emerging evidence highlights Traditional Chinese Medicine (TCM) - with its multi-target epigenetic modulatory potential - as a promising therapeutic strategy.
This review systematically evaluates the epigenetic landscape of DIC pathogenesis and critically summarizes the cardioprotective effects of TCM through epigenetic reprogramming, aiming to bridge mechanistic insights with translational opportunities.
STUDY-DESIGN/METHODS: Data for this review were sourced from various scientific databases up to March 2025. Search terms include "Doxorubicin", "Adriamycin", "Cardiotoxicity", "DOX-induced cardiotoxicity", "Doxorubicin induced cardiomyopathy", "epigenetic modifications", "Histone Modification", "DNA Methylation", "Noncoding RNAs", "long noncoding RNA", "microRNA", circular RNAs, "inflammation", "ferroptosis", "autophagy", "apoptosis" and "Traditional Chinese Medicine" as well as several combinations thereof. Exclusions comprised non-TCM interventions, studies lacking mechanistic clarity, non-cardiotoxicity endpoints, case reports, or inaccessible data.
By regulating various signaling pathways including oxidative stress, inflammation, autophagy and epigenetic modification, TCM has been positioned as a promising therapeutic strategy in alleviating DIC. We thoroughly review the pathological mechanism of DIC especially the epigenetic modification and further summarize the potential role of TCM. While preclinical data are compelling, clinical trials validating TCM's epigenetic effects (e.g., circulating miRNA biomarkers) are urgently needed.
This review synthesizes current evidence on TCM's cardioprotective effects via epigenetic modulation, providing a foundation for clinical translation.
阿霉素（DOX）是一种基石性化疗药物，受剂量依赖性心脏毒性困扰，这限制了其临床应用。尽管在理解阿霉素诱导的心脏毒性（DIC）方面取得了进展，但有效的干预措施仍然有限。新出现的证据表明，具有多靶点表观遗传调节潜力的传统中药（TCM）是一种有前景的治疗策略。
本综述系统评估DIC发病机制的表观遗传格局，并批判性地总结中药通过表观遗传重编程的心脏保护作用，旨在将机制见解与转化机会联系起来。
研究设计/方法：本综述的数据来自截至2025年3月的各种科学数据库。检索词包括“阿霉素”、“阿霉素”、“心脏毒性”、“阿霉素诱导的心脏毒性”、“阿霉素诱导的心肌病”、“表观遗传修饰”、“组蛋白修饰”、“DNA甲基化”、“非编码RNA”、“长链非编码RNA”、“微小RNA”、环状RNA、“炎症”、“铁死亡”、“自噬”、“凋亡”和“传统中药”以及它们的几种组合。排除项包括非中药干预、缺乏机制清晰度的研究、非心脏毒性终点、病例报告或无法获取的数据。
通过调节包括氧化应激、炎症、自噬和表观遗传修饰在内的各种信号通路，中药已被定位为减轻DIC的一种有前景的治疗策略。我们全面回顾了DIC的病理机制，特别是表观遗传修饰，并进一步总结了中药的潜在作用。虽然临床前数据令人信服，但迫切需要验证中药表观遗传效应（如循环微小RNA生物标志物）的临床试验。
本综述综合了目前关于中药通过表观遗传调节产生心脏保护作用的证据，为临床转化提供了基础。
