AUTHOR=Li Weili , Cao Jing , Wang Xiaoping , Zhang Yawen , Sun Qianbin , Jiang Yanyan , Yao Junkai , Li Chun , Wang Yong , Wang Wei 

TITLE=Ferruginol Restores SIRT1-PGC-1α-Mediated Mitochondrial Biogenesis and Fatty Acid Oxidation for the Treatment of DOX-Induced Cardiotoxicity

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.773834

DOI=10.3389/fphar.2021.773834

ISSN=1663-9812

ABSTRACT=Background: Doxorubicin (DOX), a broad-spectrum chemotherapy drug, have 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 DIC mouse. Whereafter, multiple methods including western blot, RT-qPCR, transmission electron microscope, CO-IP, immunofluorescence and other staining methods, and antagonist of SIRT1 and PGC1α were utilized to confirmed 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&FAO) by increasing 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 SIRT1-PGC-1α axis.