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Screening of an FDA-approved compound library identifies apigenin for the treatment of myocardial injury.

ABSTRACT: Apigenin is the active ingredient in Ludangshen. Although previous studies reported the cardioprotective actions of apigenin against doxorubicin (Dox)-induced cardiomyopathy, the underlying mechanisms remain incompletely understood. Since apigenin beneficially regulates various aspects of mitochondrial function and dynamics, we asked whether apigenin improves heart function in mice with Dox-induced cardiomyopathy by regulating the mitochondrial unfolded protein response (UPR^mt). Co-administration of apigenin significantly restored heart function, reduced myocardial swelling, inhibited cardiac inflammation, increased cardiac transcription of UPR^mt-related genes, and promoted cardiomyocyte survival in Dox-treated mice. In turn, blockade of UPR^mt abolished the mito- and cytoprotective effects of apigenin, evidenced by decreased ATP production, suppressed mitochondrial antioxidant capacity, and increased apoptosis, in Dox-treated, cultured HL-1 cardiomyocytes. Furthermore, apigenin treatment prevented Dox-induced downregulation of Sirt1 and Atf5 expression, and the beneficial effects of apigenin were completely nullified in Sirt1 knockout (KO) mice or after siRNA-mediated Sirt1 knockdown in vitro. We thus provide novel evidence for a promotive effect of apigenin on UPR^mt via regulation of the Sirt1/Atf5 pathway. Our findings uncover that apigenin seems to be an effective therapeutic agent to alleviate Dox-mediated cardiotoxicity.

SUBMITTER: Li H

PROVIDER: S-EPMC10620826 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Screening of an FDA-approved compound library identifies apigenin for the treatment of myocardial injury.

Li Haixia H Chen Dong D Zhang Xiaoqin X Chen Mingxian M Zhi Yinghao Y Cui Weilu W Li Shanshan S Xu Fan F Tan Ying Y Zhou Hao H Chang Xing X Chen Hengwen H

International journal of biological sciences 20231016 16

Apigenin is the active ingredient in Ludangshen. Although previous studies reported the cardioprotective actions of apigenin against doxorubicin (Dox)-induced cardiomyopathy, the underlying mechanisms remain incompletely understood. Since apigenin beneficially regulates various aspects of mitochondrial function and dynamics, we asked whether apigenin improves heart function in mice with Dox-induced cardiomyopathy by regulating the mitochondrial unfolded protein response (UPR<sup>mt</sup>). Co-ad ...[more]

PMID: 37928261

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Screening of an FDA-approved compound library identifies apigenin for the treatment of myocardial injury.

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Screening of an FDA-approved compound library identifies apigenin for the treatment of myocardial injury.

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