Journal of Zhejiang University SCIENCE  B

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Rhein attenuates doxorubicin-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission via the PI3K/Akt pathway


Author(s):  Huan YUE1*, Runjing LI3*, Jiajia XU4, Weixin LIU1, Ziyang ZHAO1, Junxiao FENG1, Rui SHI5, Dongkun XIE6, Zhenghao ZHANG2, Xingjuan SHI1

Affiliation(s):  1School of Life Science and Technology, Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China 2Department of Hematology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China 3Department of Geriatrics Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China 4The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361102, China 5School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China 6State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Air Force Medical University, Xi'an 710032, China

Corresponding email(s):  Zhenghao ZHANG, zhangzhenghao123@sohu.com Xingjuan SHI, xingjuanshi@seu.edu.cn

Key Words:  Rhein; Cardiotoxicity; Mitochondrial fission; Drp1; Akt


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Huan YUE1*, Runjing LI3*, Jiajia XU4, Weixin LIU1, Ziyang ZHAO1, Junxiao FENG1, Rui SHI5, Dongkun XIE6, Zhenghao ZHANG2, Xingjuan SHI1. Rhein attenuates doxorubicin-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission via the PI3K/Akt pathway[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2500658

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author="Huan YUE1*, Runjing LI3*, Jiajia XU4, Weixin LIU1, Ziyang ZHAO1, Junxiao FENG1, Rui SHI5, Dongkun XIE6, Zhenghao ZHANG2, Xingjuan SHI1",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2500658"
}

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%T Rhein attenuates doxorubicin-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission via the PI3K/Akt pathway
%A Huan YUE1*
%A Runjing LI3*
%A Jiajia XU4
%A Weixin LIU1
%A Ziyang ZHAO1
%A Junxiao FENG1
%A Rui SHI5
%A Dongkun XIE6
%A Zhenghao ZHANG2
%A Xingjuan SHI1
%J Journal of Zhejiang University SCIENCE B
%P
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%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2500658"

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T1 - Rhein attenuates doxorubicin-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission via the PI3K/Akt pathway
A1 - Huan YUE1*
A1 - Runjing LI3*
A1 - Jiajia XU4
A1 - Weixin LIU1
A1 - Ziyang ZHAO1
A1 - Junxiao FENG1
A1 - Rui SHI5
A1 - Dongkun XIE6
A1 - Zhenghao ZHANG2
A1 - Xingjuan SHI1
J0 - Journal of Zhejiang University Science B
SP -
EP -
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PB - Zhejiang University Press & Springer
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doi="https://doi.org/10.1631/jzus.B2500658"


Abstract: Mitochondrial dynamics, including mitochondrial fusion and fission, have been identified as a critical regulator of heart function. Doxorubicin (Dox) is a highly effective chemotherapeutic agent that has demonstrated broad-spectrum activity against a variety of tumor types, whereas its application is limited due to cardiotoxic effects. Rhein, a medicinal active ingredient found in rhubarb, possesses a wide range of pharmacological activities. However, whether it exerts a cardioprotective role in Dox-induced cardiotoxicity by regulating mitochondrial dynamics remains to be investigated. In this study, we found that Dox treatment promoted mitochondrial fission and elevated the expression of dynamin-related protein 1 (Drp1) in cardiomyocytes. In addition, Drp1 deletion reduced mitochondrial fission and mitochondrial ROS, and attenuated Dox-induced cardiotoxicity both in vitro and in vivo. Furthermore, rhein treatment rescued Dox-induced cardiac damage in vivo. Mechanistically, rhein attenuated Dox-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission and mitochondrial ROS in cardiomyocytes. Moreover, it alleviated the Dox-induced upregulation of Drp1 by activating phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. In conclusion, our findings demonstrate that rhein attenuates Dox-induced cardiotoxicity by regulating Drp1-mediated mitochondrial fission and mitochondrial ROS via the PI3K/Akt pathway.

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On-line Access: 2026-04-13

Received: 2025-10-20

Revision Accepted: 2026-03-18

Crosschecked: 0000-00-00

Cited: 0

Clicked: 202

Citations:  Bibtex RefMan EndNote GB/T7714

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