Protective Role of Taraxasterol against Cardiovascular Aging and Aging-Induced Desensitization of Insulin Signaling.

ABSTRACT

BACKGROUND: Cardiovascular disease (CVD) has become one of the leading causes of death and disability worldwide, and its incidence continues to increase because of an aging population. Studies have shown that the function of cardiomyocytes decreases during aging, leading to changes in the functional and structural integrity of the heart, ultimately resulting in CVD. The decrease in the number of functional cardiomyocytes has a negative impact on cardiac function; thus, myocardial aging is one of the main factors that causes heart-related diseases (such as CVD). Therefore, alleviating cardiac aging is one of the main ways of treating aging-related cardiac diseases. In this study, we evaluated the potential effect of taraxasterol on myocardial aging. METHODS: The effect of taraxasterol on the aging of cardiomyocytes was analyzed in vivo and in vitro using a D-galactose treatment mouse model of cardiomyocyte senescence. Furthermore, the effect of taraxasterol on aging-induced desensitization of insulin signaling was also evaluated. RESULTS: The experimental results indicated that taraxasterol could reduce cardiomyocyte senescence, which was evaluated using Sa-ß-gal staining and senescence-related marker molecules (e.g., p16 and p21). We found that taraxasterol could significantly alleviate cardiomyocyte senescence in the in vitro cell model. Furthermore, we found that taraxasterol had the potential to alleviate cardiomyocyte senescence via the regulation of oxidative stress and inflammatory processes. Additionally, taraxasterol could relieve the desensitization of insulin signaling caused by aging. Finally, we showed that cardiovascular aging and fibrosis were alleviated by taraxasterol treatment in vivo. CONCLUSIONS: Taken together, this work illustrated that taraxasterol could reduce cardiac aging and fibrosis and enhance insulin signaling sensitivity, indicating that taraxasterol may be an effective drug or health food additive for treating cardiac aging and fibrosis.