Ferruginol Restores SIRT1-PGC-1α-Mediated Mitochondrial Biogenesis and Fatty Acid Oxidation for the Treatment of DOX-Induced Cardiotoxicity
Background: Doxorubicin (DOX), a broad-spectrum chemotherapy drug, has life-threatening cardiotoxicity. Therefore, searching cardioprotective drugs for DOX-induced cardiotoxicity (DIC) is urgently needed.Objectives: This study aimed to explore cardioprotective effect and specific mechanism by which...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:7e24a20cbcc8455980b15b5ebefa58132021-11-30T18:58:41ZFerruginol Restores SIRT1-PGC-1α-Mediated Mitochondrial Biogenesis and Fatty Acid Oxidation for the Treatment of DOX-Induced Cardiotoxicity1663-981210.3389/fphar.2021.773834https://doaj.org/article/7e24a20cbcc8455980b15b5ebefa58132021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.773834/fullhttps://doaj.org/toc/1663-9812Background: Doxorubicin (DOX), a broad-spectrum chemotherapy drug, has life-threatening cardiotoxicity. Therefore, searching cardioprotective drugs for DOX-induced cardiotoxicity (DIC) is urgently needed.Objectives: This study aimed to explore cardioprotective effect and specific mechanism by which Ferruginol (FGL) attenuated DIC in vivo and in vitro.Methods: We evaluated the cardioprotection of FGL and performed high-throughput RNA-Seq on a DIC mouse. Whereafter, multiple methods, including western blot, RT-qPCR, a transmission electron microscope, CO-IP, immunofluorescence, and other staining methods, and antagonist of SIRT1 and PGC-1α were utilized to confirm the cardioprotection and molecular mechanism of FGL.Results: FGL-exerted cardioprotection manifested as enhanced cardiac function and reduced structural damage and apoptosis. The transcriptome and other results revealed that FGL facilitated PGC-1α-mediated mitochondrial biogenesis and fatty acid oxidation (MB and FAO) by increasing the expression of PGC-1α and concurrently promoting the expression of SIRT1-enhancing deacetylase SIRT1 deacetylating and activating PGC-1α.Conclusions: These results documented that FGL exerted cardioprotective effects restoring MB&FAO via the SIRT1–PGC-1α axis.Weili LiJing CaoXiaoping WangYawen ZhangQianbin SunYanyan JiangJunkai YaoChun LiYong WangYong WangWei WangWei WangWei WangFrontiers Media S.A.articleferruginolmitochondrial biogenesisfatty acid oxidationSIRT1PGC-1αdoxorubicinTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
ferruginol mitochondrial biogenesis fatty acid oxidation SIRT1 PGC-1α doxorubicin Therapeutics. Pharmacology RM1-950 |
| spellingShingle |
ferruginol mitochondrial biogenesis fatty acid oxidation SIRT1 PGC-1α doxorubicin Therapeutics. Pharmacology RM1-950 Weili Li Jing Cao Xiaoping Wang Yawen Zhang Qianbin Sun Yanyan Jiang Junkai Yao Chun Li Yong Wang Yong Wang Wei Wang Wei Wang Wei Wang Ferruginol Restores SIRT1-PGC-1α-Mediated Mitochondrial Biogenesis and Fatty Acid Oxidation for the Treatment of DOX-Induced Cardiotoxicity |
| description |
Background: Doxorubicin (DOX), a broad-spectrum chemotherapy drug, has life-threatening cardiotoxicity. Therefore, searching cardioprotective drugs for DOX-induced cardiotoxicity (DIC) is urgently needed.Objectives: This study aimed to explore cardioprotective effect and specific mechanism by which Ferruginol (FGL) attenuated DIC in vivo and in vitro.Methods: We evaluated the cardioprotection of FGL and performed high-throughput RNA-Seq on a DIC mouse. Whereafter, multiple methods, including western blot, RT-qPCR, a transmission electron microscope, CO-IP, immunofluorescence, and other staining methods, and antagonist of SIRT1 and PGC-1α were utilized to confirm the cardioprotection and molecular mechanism of FGL.Results: FGL-exerted cardioprotection manifested as enhanced cardiac function and reduced structural damage and apoptosis. The transcriptome and other results revealed that FGL facilitated PGC-1α-mediated mitochondrial biogenesis and fatty acid oxidation (MB and FAO) by increasing the expression of PGC-1α and concurrently promoting the expression of SIRT1-enhancing deacetylase SIRT1 deacetylating and activating PGC-1α.Conclusions: These results documented that FGL exerted cardioprotective effects restoring MB&FAO via the SIRT1–PGC-1α axis. |
| format |
article |
| author |
Weili Li Jing Cao Xiaoping Wang Yawen Zhang Qianbin Sun Yanyan Jiang Junkai Yao Chun Li Yong Wang Yong Wang Wei Wang Wei Wang Wei Wang |
| author_facet |
Weili Li Jing Cao Xiaoping Wang Yawen Zhang Qianbin Sun Yanyan Jiang Junkai Yao Chun Li Yong Wang Yong Wang Wei Wang Wei Wang Wei Wang |
| author_sort |
Weili Li |
| title |
Ferruginol Restores SIRT1-PGC-1α-Mediated Mitochondrial Biogenesis and Fatty Acid Oxidation for the Treatment of DOX-Induced Cardiotoxicity |
| title_short |
Ferruginol Restores SIRT1-PGC-1α-Mediated Mitochondrial Biogenesis and Fatty Acid Oxidation for the Treatment of DOX-Induced Cardiotoxicity |
| title_full |
Ferruginol Restores SIRT1-PGC-1α-Mediated Mitochondrial Biogenesis and Fatty Acid Oxidation for the Treatment of DOX-Induced Cardiotoxicity |
| title_fullStr |
Ferruginol Restores SIRT1-PGC-1α-Mediated Mitochondrial Biogenesis and Fatty Acid Oxidation for the Treatment of DOX-Induced Cardiotoxicity |
| title_full_unstemmed |
Ferruginol Restores SIRT1-PGC-1α-Mediated Mitochondrial Biogenesis and Fatty Acid Oxidation for the Treatment of DOX-Induced Cardiotoxicity |
| title_sort |
ferruginol restores sirt1-pgc-1α-mediated mitochondrial biogenesis and fatty acid oxidation for the treatment of dox-induced cardiotoxicity |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/7e24a20cbcc8455980b15b5ebefa5813 |
| work_keys_str_mv |
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1718406334245765120 |