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

Li, Haixia1; Chen, Dong2; Zhang, Xiaoqin3; Chen, Mingxian4; Zhi, Yinghao5; Cui, Weilu1; Li, Shanshan1; Xu, Fan1; Tan, Ying6; Zhou, Hao6; Chang, Xing1; Chen, Hengwen1

2023

10.7150/ijbs.85204

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES   Impact Factor & Quartile

1449-2288

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 (UPRmt). Co-administration of apigenin significantly restored heart function, reduced myocardial swelling, inhibited cardiac inflammation, increased cardiac transcription of UPRmt-related genes, and promoted cardiomyocyte survival in Dox-treated mice. In turn, blockade of UPRmt 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 UPRmt via regulation of the Sirt1/Atf5 pathway. Our findings uncover that apigenin seems to be an effective therapeutic agent to alleviate Dox-mediated cardiotoxicity.

apigenin doxorubicin mitochondrial unfolded protein response Sirt1 Atf5 cardiomyopathy

SCI

English

Others

Beijing Natural Science Foundation[7222166] ; National Natural Science Foundation of China["8187142391","81973682","82200091","82370083"] ; National Social Science Foundation of China[21VJXG037]

Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics

Biochemistry & Molecular Biology ; Biology

WOS:001089330300003

IVYSPRING INT PUBL

Web of Science

1.China Acad Chinese Med Sci, Guanganmen Hosp, Beijing 100053, Peoples R China
2.Beijing Univ Tradit Chinese Med, Dongzhimen Hosp, Beijing 100000, Peoples R China
3.Beijing Univ Chinese Med, Beijing 100029, Peoples R China
4.Zhejiang Tongde Hosp, Hangzhou 310012, Peoples R China
5.Zhejiang Chinese Med Univ, Wenzhou Hosp TCM, Wenzhou 325000, Peoples R China
6.Southern Univ Sci & Technol SUSTech, Sch Med, Shenzhen, Guangdong, Peoples R China

Li, Haixia,Chen, Dong,Zhang, Xiaoqin,et al. Screening of an FDA-approved compound library identifies apigenin for the treatment of myocardial injury[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2023,19(16).

Li, Haixia.,Chen, Dong.,Zhang, Xiaoqin.,Chen, Mingxian.,Zhi, Yinghao.,...&Chen, Hengwen.(2023).Screening of an FDA-approved compound library identifies apigenin for the treatment of myocardial injury.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,19(16).

Li, Haixia,et al."Screening of an FDA-approved compound library identifies apigenin for the treatment of myocardial injury".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 19.16(2023).