Research Paper Volume 15, Issue 19 pp 10133—10145

Sheng-Mai-Yin inhibits doxorubicin-induced ferroptosis and cardiotoxicity through regulation of Hmox1

Peina Meng1,4, *, , Zhaoyang Chen2, *, , Tianhui Sun1,2, *, , Lili Wu3, , Yifan Wang2, , Tianwei Guo2, , Jin Yang2, , Jiebin Zhu1,2, ,

  • 1 Department of Preventive Medicine, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, China
  • 2 School of Traditional Chinese Medicine and School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
  • 3 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
  • 4 Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
* Equal contribution

Received: March 11, 2023       Accepted: September 2, 2023       Published: September 28, 2023
How to Cite

Copyright: © 2023 Meng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Doxorubicin (DOX) is a potent chemotherapeutic drug used for treating various cancers. However, its clinical use is limited due to its severe cardiotoxicity, which often results in high mortality rates. Sheng-Mai-Yin (SMY), a Traditional Chinese medicine (TCM) prescription, has been reported to exert a cardioprotective effect in various cardiovascular diseases, including DOX-induced cardiotoxicity (DIC). This study aimed to provide novel insights into the underlying cardioprotective mechanism of SMY. SMY, composed of Codonopsis pilosula (Franch.), Ophiopogon japonicus (Thunb.), and Schisandra chinensis (Turcz.) at a ratio of 3:2:1, was intragastrically administered to male C57BL/6 mice for five days prior to the intraperitoneal injection of mitoTEMPO. One day later, DOX was intraperitoneally injected. Hematoxylin-eosin staining and Sirius red staining were carried out to estimate the pharmacological effect of SMY on cardiotoxicity. Mitochondrial function and ferroptosis biomarkers were also examined. AAV was utilized to overexpress Hmox1 to confirm whether Hmox1-mediated ferroptosis is associated with the cardioprotective effect of SMY on DOX-induced cardiotoxicity. The findings revealed that SMY therapy reduced the number of damaged cardiomyocytes. SMY therapy also reversed the inductions of cardiac MDA, serum MDA, LDH, and CK-MB contents, which dramatically decreased nonheme iron levels. In the meantime, SMY corrected the changes to ferroptosis indices brought on by DOX stimulation. Additionally, Hmox1 overexpression prevented SMY's ability to reverse cardiotoxicity. Our results showed that SMY effectively restrained lipid oxidation, reduced iron overload, and inhibited DOX-induced ferroptosis and cardiotoxicity, possibly via the mediation of Hmox1.


DOX: doxorubicin; TCM: Traditional Chinese medicine; SMY: Sheng-Mai-Yin; DIC: doxorubicin-induced cardiotoxicity; Hmox1: heme oxygenase 1; RCD: regulated cell death; ROS: reactive oxygen species; FTH1: ferritin heavy chain; TFR1: transferrin receptor 1; GPX4: glutathione peroxidase 4; MDA: malondialdehyde; LDH: lactate dehydrogenase; CK-MB: creatine kinase-mb; Nrf2: nuclear factor erythroid 2-related factor 2; AAV: adeno-associated virus.