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

Overview

Journal Front Pharmacol

Date 2021 Dec 13

PMID 34899332

Citations 14

Authors

Weili Li

Jing Cao

Xiaoping Wang

Yawen Zhang

Qianbin Sun

Yanyan Jiang

Junkai Yao

Chun Li

Yong Wang

Wei Wang

Affiliations

Soon will be listed here.

Abstract

Doxorubicin (DOX), a broad-spectrum chemotherapy drug, has life-threatening cardiotoxicity. Therefore, searching cardioprotective drugs for DOX-induced cardiotoxicity (DIC) is urgently needed. This study aimed to explore cardioprotective effect and specific mechanism by which Ferruginol (FGL) attenuated DIC and . 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. 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. These results documented that FGL exerted cardioprotective effects restoring MB&FAO via the SIRT1-PGC-1α axis.

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