RESUMO
BACKGROUND: YangXinDingJi (YXDJ) capsule is one of traditional Chinese medicines (TCMs) derived from Zhigancao decoction, which is usually used for the treatment of cardiovascular disease in China. Aim of the Study. Cardiovascular events are one of the leading causes of death worldwide. Myocardial ischemia (MI) severely reduces myocyte longevity and function. The YangXinDingJi (YXDJ) capsule has been used in the treatment of clinical cardiac disease in China. Nevertheless, the underlying cellular mechanisms for the benefits to heart function resulting from the use of this capsule are still unclear. The aim of this study was to evaluate the protective effects of the YXDJ on isoprenaline-induced MI in rats and to clarify its underlying myocardial protective mechanisms based on L-type calcium channels and myocardial contractility. MATERIALS AND METHODS: Rats were randomly divided into five groups with ten rats in each group: (1) control; (2) ISO-induced model; (3) high-dose YXDJ (2.8 g/kg/day intraperitoneally for five days), (4) low-dose YXDJ (1.4 g/kg/day for five days); and (5) verapamil (n = 10 in each group). Isoproterenol (ISO) was injected subcutaneously for two consecutive days to induce the rat model of MI. Heart and biochemical parameters were obtained. The patch-clamp technique was used to observe the regulatory effects of YXDJ on the L-type calcium current (ICa-L) in isolated cardiomyocytes. An IonOptix MyoCam detection system was used to observe the contractility of YXDJ on isolated cardiomyocytes. RESULTS: YXDJ caused a significant improvement in pathological heart morphology and alleviated oxidative stress and inflammatory responses. Exposure to YXDJ caused a decrease in blockade of ICa-L in a concentration-dependent manner. CONCLUSIONS: The results indicate that YXDJ significantly inhibited inflammatory cytokine expressions, oxidative stress, and L-type Ca2+ channels, and decreased contractility in isolated rat cardiomyocytes. These findings may be relevant to the cardioprotective efficacy of YXDJ.
RESUMO
Ginger has been widely used as a flavor, food, and traditional medicine for centuries. 6-Gingerol (6-Gin) is the active components of ginger and offers some beneficial effects on cardiovascular diseases. Here, the effects of 6-Gin on L-type Ca2+ current (ICa-L), contractility, and the Ca2+ transients of rat cardiomyocytes, were investigated via patch-clamp technique and the Ion Optix system. The 6-Gin decreased the ICa-L of normal and ischemic ventricular myocytes by 58.17 ± 1.05% and 55.22 ± 1.34%, respectively. 6-Gin decreased ICa-L in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50) of 31.25 µmol/L. At 300 µmol/L, 6-Gin reduced the cell shortening by 48.87 ± 5.44% and the transients by 42.5 ± 9.79%. The results indicate that the molecular mechanisms underlying the cardio-protective effects of 6-Gin may because of a decreasing of intracellular Ca2+ via the inhibition of ICa-L and contractility in rat cardiomyocytes.
RESUMO
The RhoA/Rho-kinase cascade plays an important role in many aspects of cardiovascular function. This study aims to investigate the protective effects of fasudil, a Rho-kinase inhibitor, on pressure overload induced heart failure in rats. Pressure overload induced heart failure was induced in SD rats by banding the abdominal aorta for 8 weeks. The rats were divided into four groups: Sham, TAC, TAC plus low dose of fasudil, and TAC plus high dose of fasudil group. Low dose and high dose fasudil were 5 and 10 mg/kg/day, respectively. Rats in the Sham and TAC groups were treated with vehicle. Fasudil effectively inhibited TAC-induced heart failure, as evaluated by echocardiography and transmission electron microscopy. Fasudil could significantly promote superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity and significantly decrease malondialdehyde (MDA) content in a dose-dependent maner in TAC rats. Consistently, fasudil evoked significant nuclear translocation of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) with increased DNA/promoter binding and transactivation of Nrf2 targets. In addition, fasudil increased the content of iron as well as transferrin receptor 1 (TfR1) in TAC rats. A mild oxidative stress induced by iron may activate the antioxidant enzymes by feedback response. Taken together, these results indicate that the protective effect of fasudil may be due to its strong antioxidative activities which related with the activated Nrf2 and its down-regulated genes. These findings provide a new treatment concept and support the benefit of fasudil treatment in heart failure.