School of Basic Medicine, Research Center of Integrative Medicine, Guangzhou University of Chinese Medicine, 230 Guangzhou University City Outer Ring Road, Guangzhou, 510006, China.
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan, 430030, China.
Sci Rep. 2017 Sep 20;7(1):11989. doi: 10.1038/s41598-017-12095-y.
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.
和厚朴酚是一种药用植物厚朴树皮的主要成分。和厚朴酚对许多疾病状况，特别是癌症具有潜在的药理益处。最近的研究表明，和厚朴酚通过线粒体蛋白的去乙酰化作用对心肌肥大和阿霉素（Dox）心脏毒性发挥有益作用。然而，和厚朴酚对心脏线粒体呼吸的影响和机制仍不清楚。在本研究中，我们研究了和厚朴酚对 Dox 处理小鼠心脏线粒体呼吸的影响。用和厚朴酚处理的小鼠新鲜分离的线粒体中的耗氧量显示出增强的线粒体呼吸。与对照组小鼠相比，和厚朴酚处理小鼠的 Dox 诱导的线粒体呼吸损伤不那么明显。此外，荧光素酶报告基因检测显示和厚朴酚在培养的大鼠胚胎心肌细胞（H9c2）中适度增加了 PPARγ 的转录活性。和厚朴酚上调了小鼠心脏中的 PPARγ 表达。和厚朴酚抑制了 Dox 处理小鼠的心脏炎症反应和氧化应激。结果，和厚朴酚通过抑制心脏线粒体蛋白乙酰化和增强 PPARγ 活性来改善心脏功能和减少心肌细胞凋亡，从而减轻 Dox 心脏毒性。我们得出结论，和厚朴酚通过抑制心脏线粒体蛋白乙酰化和增强心脏中的 PPARγ 活性来改善线粒体功能，从而保护心脏免受 Dox 心脏毒性。这项研究进一步支持和厚朴酚作为接受 Dox 治疗的癌症患者的有前途的治疗方法。
