3,4-Dihydroxybenzalacetone (DBL) Prevents Aging-Induced Myocardial Changes in Senescence-Accelerated Mouse-Prone 8 (SAMP8) Mice

Abstract

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 Inonotus obliquus (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.

The Establishment of a Mouse Model for Degenerative Kyphoscoliosis Based on Senescence-Accelerated Mouse Prone 8

“…Recently, SAMP8 mice have attracted the attention of gerontological studies due to their characteristic learning and memory impairment in old age [ 26 ]. SAMP8 mice are widely used in the study of aging-related diseases such as AD [ 27 ], cardiovascular disease [ 28 ], and age-related hearing loss [ 29 ]. More importantly, when SAMP8 mice underwent ovariectomy (OVX-SAMP8) 4 months after birth, osteoporosis was rapidly induced and bone mineral content was greatly reduced [ 30 ].…”

A review on the cultivation, bioactive compounds, health-promoting factors and clinical trials of medicinal mushrooms Taiwanofungus camphoratus, Inonotus obliquus and Tropicoporus linteus

“…A catechol-containing phenylpropanoid derivative found in T. linteus , 3,4-dihydroxybenzalacetone (Osmundacetone) ( 93 ), has been shown to attenuate inflammation [ 154 ], exert antioxidant activities [ 155 ], suppress the metastasis and formation of cancer [ 156 ], and protect against aging-associated myocardial alterations [ 157 ]. Osmundacetone ( 93 ) and inotilone ( 142 ), have also been isolated from T. linteus , where they have been demonstrated to have antioxidant properties [ 158 ] and inhibit neuraminidase activity to thus exert an antiviral effect [ 13 ].…”

Molecular Mechanisms to Target Cellular Senescence in Aging and Disease

“…An alternative strategy could be to prevent senescent cells accumulation, for example, by using molecules capable of inhibiting oxidative stress and inflammatory status, such as 3,4-Dihydroxybenzalacetone (DBL), which has shown in vivo cardioprotective potential against age-associated cardiac changes [ 7 ], or by using inhibitors of inflammatory mediators that promote cellular senescence, such as visfatin. Visfatin, firstly identified as an adipocytokine released by visceral adipose tissue, was short after reconsidered as a more widely secreted factor and it has been proposed among the factors able to induce senescence in human dental pulp cells [ 8 ], as well as in human endothelial cells [ 9 ].…”