Asiatic Acid Protects against Doxorubicin-Induced Cardiotoxicity in Mice

Abstract

The use of doxorubicin (DOX) can result in depression of cardiac function and refractory cardiomyopathy. Currently, there are no effective approaches to prevent DOX-related cardiac complications. Asiatic acid (AA) has been reported to provide cardioprotection against several cardiovascular diseases. However, whether AA could attenuate DOX-related cardiac injury remains unclear. DOX (15 mg/kg) was injected intraperitoneally into the mice to mimic acute cardiac injury, and the mice were given AA (10 mg/kg or 30 mg/kg) for 2 weeks for protection. The data in our study found that AA-treated mice exhibited attenuated cardiac injury and improved cardiac function in response to DOX injection. AA also suppressed myocardial oxidative damage and apoptosis without affecting cardiac inflammation in DOX-treated mice. AA also provided protection in DOX-challenged cardiomyocytes, improved cell viability, and suppressed intracellular reactive oxygen species (ROS) in vitro. Detection of signaling pathways showed that AA activated protein kinase B (AKT) signaling pathway in vivo and in vitro. Furthermore, we found that AA lost its protective effects in the heart with AKT inactivation. In conclusion, our results found that AA could attenuate DOX-induced myocardial oxidative stress and apoptosis via activation of the AKT signaling pathway.

Analysis of Models of Doxorubicin-Induced Cardiomyopathy in Rats and Mice. A Modern View From the Perspective of the Pathophysiologist and the Clinician

“…In current experimental practice mouse models are used either for acute (with one-time high dose administration) or chronic (with serial administration until the cumulative dose has been achieved) DOX cardiomyopathy modeling ( Hullin et al, 2018 ; Bai and Wang, 2019 ; Gioffré et al, 2019 ; Hu et al, 2020 ; Peres Diaz et al, 2020 ). It is worth noting that an important criterion for the model quality is the animal survival rate.…”

Using integrated GC-MS analysis, in vitro experiments, network pharmacology: exploring migao fatty oil active components/mechanisms against coronary heart disease

“…For example, AKT1 was the major AKT isoform in the heart and blood vessels, and the activation of AKT1 was associated with inflammation, oxidative stress, accumulation of oxidized lipids, and formed a positive feedback loop exacerbating the consequences of oxidative stress. Interfering with Akt1 signalling in vivo may therefore protect and improve survival under dyslipidaemia by reducing oxidative stress and the response to oxidized lipids (Wang et al, 2022a;Hu et al, 2020). Atherosclerosis is a chronic inflammatory condition in which lipid-rich plaques in the walls of arteries result in constriction.…”

Protective Effect of Natural Medicinal Plants on Cardiomyocyte Injury in Heart Failure: Targeting the Dysregulation of Mitochondrial Homeostasis and Mitophagy

“…Asiatic Acid. Disturbed cardiomyocyte energy metabolism is a major factor in the pathology of heart failure, which may ultimately lead to a poor prognosis [145]. Mitophagy is important in regulating the mitochondrial respiratory chain function and ATP production.…”