Translational Psychiatry Program, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA.
Faculty of Applied Life Sciences, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences Niigata, Niigata 956-8603, Japan.
Cells. 2020 Mar 3;9(3):597. doi: 10.3390/cells9030597.
Aging is a predominant risk factor for the development and progression of cardiovascular complications. Physiologically and anatomically, the heart undergoes numerous changes that result in poor cardiac function in the elderly population. Recently, several studies have provided promising results, confirming the ability of the senescence-accelerated mouse-prone 8 (SAMP8) model to accurately model age-related cardiovascular alterations. In this study, using a murine model of senescence, SAMP8, we aimed to investigate the effect of 3,4-dihydroxybenzalacetone (DBL), a catechol-containing phenylpropanoid derivative isolated from (Chaga), on cardiac aging. DBL was administered at the doses of 10 mg/kg and 20 mg/kg by oral gavage to SAMP8 mice to examine aging-mediated cardiac changes, such as oxidative DNA damage, oxygen radical antioxidant capacity (ORAC) value, fibrosis, inflammation, and apoptosis. The treatment with DBL at both doses significantly reduced aging-mediated oxidative DNA damage, and simultaneously increased the ORAC value in the SAMP8 assay. Cardiac fibrosis was assessed with Azan-Mallory staining, and the number of cardiac remodeling markers was found to be significantly reduced after the treatment with DBL. We also observed a decrease in cardiomyocyte apoptosis as measured by the terminal transferase-mediated dUTP nick end labeling (TUNEL) staining method and the caspase-3 levels in SAMP8 mice compared with senescence-resistant control (SAMR1) mice. The findings from this study suggest that DBL has a potentially beneficial effect on aging-mediated myocardial alterations. Further studies are warranted to confirm the promising potential of this catechol compound against aging-associated myocardial dysfunction.
衰老是心血管并发症发生和发展的主要危险因素。从生理学和解剖学角度来看，心脏会发生许多变化，导致老年人群的心脏功能不佳。最近，多项研究提供了有希望的结果，证实了加速衰老小鼠-prone 8（SAMP8）模型能够准确模拟与年龄相关的心血管改变。在这项研究中，我们使用衰老的小鼠模型 SAMP8，旨在研究 3,4-二羟基苯甲酰丙酮（DBL）对心脏衰老的影响，DBL 是从（Chaga）中分离出来的含儿茶酚的苯丙素衍生物。通过口服灌胃给予 SAMP8 小鼠 10mg/kg 和 20mg/kg 的 DBL 剂量，以检查衰老介导的心脏变化，如氧化 DNA 损伤、氧自由基抗氧化能力（ORAC）值、纤维化、炎症和细胞凋亡。两种剂量的 DBL 治疗均显著降低了衰老介导的氧化 DNA 损伤，同时增加了 SAMP8 测定中的 ORAC 值。用阿赞-马洛里染色评估心脏纤维化，发现 DBL 治疗后心脏重构标志物的数量明显减少。通过末端转移酶介导的 dUTP 缺口末端标记（TUNEL）染色法和 caspase-3 水平观察到心肌细胞凋亡减少。与衰老抗性对照（SAMR1）小鼠相比，SAMP8 小鼠中。这项研究的结果表明，DBL 对衰老介导的心肌改变具有潜在的有益作用。需要进一步的研究来证实这种儿茶酚化合物对与衰老相关的心肌功能障碍的有希望的潜力。
