Honokiol protects against doxorubicin cardiotoxicity via improving mitochondrial function in mouse hearts.
Lizhen HuangKailiang ZhangYingying GuoFengyuan HuangKevin YangLong ChenKai HuangFengxue ZhangQinqiang LongQinglin YangPublished in: Scientific reports (2017)
Honokiol is a key component of a medicinal herb, Magnolia bark. Honokiol possesses potential pharmacological benefits for many disease conditions, especially cancer. Recent studies demonstrate that Honokiol exerts beneficial effects on cardiac hypertrophy and doxorubicin (Dox)-cardiotoxicity via deacetylation of mitochondrial proteins. However, the effects and mechanisms of Honokiol on cardiac mitochondrial respiration remain unclear. In the present study, we investigate the effect of Honokiol on cardiac mitochondrial respiration in mice subjected to Dox treatment. Oxygen consumption in freshly isolated mitochondria from mice treated with Honokiol showed enhanced mitochondrial respiration. The Dox-induced impairment of mitochondrial respiration was less pronounced in honokiol-treated than control mice. Furthermore, Luciferase reporter assay reveals that Honokiol modestly increased PPARγ transcriptional activities in cultured embryonic rat cardiomyocytes (H9c2). Honokiol upregulated the expression of PPARγ in the mouse heart. Honokiol repressed cardiac inflammatory responses and oxidative stress in mice subjected to Dox treatment. As a result, Honokiol alleviated Dox-cardiotoxicity with improved cardiac function and reduced cardiomyocyte apoptosis. We conclude that Honokiol protects the heart from Dox-cardiotoxicity via improving mitochondrial function by not only repressing mitochondrial protein acetylation but also enhancing PPARγ activity in the heart. This study further supports Honokiol as a promising therapy for cancer patients receiving Dox treatment.
Keyphrases
- oxidative stress
- heart failure
- diabetic rats
- left ventricular
- high fat diet induced
- type diabetes
- cell death
- gene expression
- squamous cell carcinoma
- drug delivery
- insulin resistance
- atrial fibrillation
- young adults
- poor prognosis
- induced apoptosis
- endothelial cells
- fatty acid
- skeletal muscle
- small molecule
- amino acid
- cancer therapy
- drug induced
- reactive oxygen species
- angiotensin ii
- protein protein