1. Academic Validation
  2. Isodunnianol alleviates doxorubicin-induced myocardial injury by activating protective autophagy

Isodunnianol alleviates doxorubicin-induced myocardial injury by activating protective autophagy

  • Food Funct. 2019 May 22;10(5):2651-2657. doi: 10.1039/c9fo00063a.
Can Chen 1 Li Jiang Min Zhang Xiaoli Pan Cheng Peng Wei Huang Qinglin Jiang
Affiliations

Affiliation

  • 1 The First Affiliated Hospital, Sichuan Province College Key Laboratory of Structure-Specific Small Molecule Drugs, School of Pharmacy, Chengdu Medical College, Chengdu 610500, China. jql_cmc@163.com.
Abstract

Recurrent cardiotoxicity limits the clinical application of doxorubicin (DOX); however the detailed molecular mechanism of DOX cardiotoxicity remains unclear. In the current study, we found that a natural product extracted from Illicium verum, isodunnianol (IDN), mitigates DOX-induced cardiotoxicity by regulating Autophagy and Apoptosis both in vitro and in vivo. DOX suppressed protective Autophagy and induced Apoptosis in H9C2 cardiac myoblasts. Additionally, IDN demonstrated up-regulated Autophagy and reduced Apoptosis through the activation of the AMPK-ULK1 pathway. In addition, the beneficial effects of IDN on DOX which induced myocardial injury were dependent on AMPK and ULK1 phosphorylation. Similar results were also observed in a DOX-induced cardiotoxicity rat model. The combination of IDN and DOX resulted in decreased Apoptosis and inflammatory myocardial fibrosis compared to the DOX mono-treatment group. In summary, our findings provide novel insights into the prevention of DOX-related toxicity by isodunnianol, a food source natural product, warranting further investigation.

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