Key result
Isodunnianol mitigated doxorubicin-induced cardiotoxicity in vitro and in a rat model by reducing apoptosis and inflammatory myocardial fibrosis via activation of the AMPK-ULK1 pathway.
Why the study?
Recurrent cardiotoxicity limits the clinical application of doxorubicin, but the detailed molecular mechanism of this cardiotoxicity remains unclear.
Does isodunnianol alleviate doxorubicin-induced myocardial injury in preclinical models?
Does isodunnianol alleviate doxorubicin-induced myocardial injury in preclinical models?
Isodunnianol mitigates doxorubicin-induced cardiotoxicity by up-regulating protective autophagy and reducing apoptosis via the AMPK-ULK1 pathway in preclinical models.
Isodunnianol attenuates doxorubicin cardiotoxicity in rats; hypothesis-generating and should not change practice pending human trials.
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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Chen et al. (2019) studied Doxorubicin-induced cardiotoxicity. Isodunnianol (IDN) vs. Doxorubicin (DOX) mono-treatment was evaluated on Apoptosis and inflammatory myocardial fibrosis. Isodunnianol mitigated doxorubicin-induced cardiotoxicity in vitro and in a rat model by reducing apoptosis and inflammatory myocardial fibrosis via activation of the AMPK-ULK1 pathway.
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