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Cynaroside regulates the AMPK/SIRT3/Nrf2 pathway to inhibit doxorubicin-induced cardiomyocyte pyroptosis
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Hai ZOU, Mengyu ZHANG, Xue YANG, Huafeng SHOU, Zhenglin CHEN, Quanfeng ZHU, Ting LUO, Xiaozhou MOU, Xiaoyi CHEN. Cynaroside regulates the AMPK/SIRT3/Nrf2 pathway to inhibit doxorubicin-induced cardiomyocyte pyroptosis[J]. Journal of Zhejiang University Science B, 1998, -1(-1): .
@article{title="Cynaroside regulates the AMPK/SIRT3/Nrf2 pathway to inhibit doxorubicin-induced cardiomyocyte pyroptosis",
author="Hai ZOU, Mengyu ZHANG, Xue YANG, Huafeng SHOU, Zhenglin CHEN, Quanfeng ZHU, Ting LUO, Xiaozhou MOU, Xiaoyi CHEN",
journal="Journal of Zhejiang University Science B",
volume="-1",
number="-1",
pages="",
year="1998",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300691"
}
%0 Journal Article
%T Cynaroside regulates the AMPK/SIRT3/Nrf2 pathway to inhibit doxorubicin-induced cardiomyocyte pyroptosis
%A Hai ZOU
%A Mengyu ZHANG
%A Xue YANG
%A Huafeng SHOU
%A Zhenglin CHEN
%A Quanfeng ZHU
%A Ting LUO
%A Xiaozhou MOU
%A Xiaoyi CHEN
%J Journal of Zhejiang University SCIENCE B
%V -1
%N -1
%P
%@ 1673-1581
%D 1998
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300691
TY - JOUR
T1 - Cynaroside regulates the AMPK/SIRT3/Nrf2 pathway to inhibit doxorubicin-induced cardiomyocyte pyroptosis
A1 - Hai ZOU
A1 - Mengyu ZHANG
A1 - Xue YANG
A1 - Huafeng SHOU
A1 - Zhenglin CHEN
A1 - Quanfeng ZHU
A1 - Ting LUO
A1 - Xiaozhou MOU
A1 - Xiaoyi CHEN
J0 - Journal of Zhejiang University Science B
VL - -1
IS - -1
SP -
EP -
%@ 1673-1581
Y1 - 1998
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300691
Abstract: 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) mice 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, 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 NLRP3, Caspase-1 and GSDMD. Mechanistically, for DOX-induced myocardial injury, Cyn could significantly modulate the expression of pivotal genes, including AMPK, PGC-1α, Sirt3, and Nrf2, which we attribute to the mediation of AMPK/Sirt3/Nrf2 pathway, which plays a central role in countering doxorubicin-induced cardiomyocyte injury. In conclusion, the present study confirms the therapeutic potential of Cyn in DIC by regulating the AMPK/SIRT3/Nrf2 pathway.
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