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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.

Arsenic trioxide (ATO)-induced hepatotoxicity limits the therapeutic effect of acute myelogenous leukemia treatment. Magnesium isoglycyrrhizinate (MgIG) is a natural compound extracted from licorice and a hepatoprotective drug used in liver injury. It exhibits anti-oxidant, anti-inflammatory and anti-apoptotic properties. The aim of the present study was to identify the protective action and underlying mechanism of MgIG against ATO-induced hepatotoxicity. A total of 50 mice were randomly divided into five groups (n=10/group): Control; ATO; MgIG and high-and low-dose MgIG + ATO. Following continuous administration of ATO for 7 days, the relative weight of the liver, liver enzyme, histological data, antioxidant enzymes, pro-inflammatory cytokines, cell apoptosis and changes in Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) signaling pathway were observed. MgIG decreased liver injury, decreased the liver weight and liver index, inhibited oxidative stress and decreased the activity of glutathione, superoxide dismutase and catalase, production of reactive oxygen species and levels of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α. Western blotting showed a decrease in Bax and caspase-3. There was decreased cleaved caspase-3 expression and increased Bcl-2 expression. MgIG notably activated ATO-mediated expression of Keap1 and Nrf2 in liver tissue. MgIG administration was an effective treatment to protect the liver from ATO-induced toxicity. MgIG maintained the level of Nrf2 in the liver and protected the antioxidative defense system to attenuate oxidative stress and prevent ATO-induced liver injury.

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 Ca 2+ current (I Ca‐L ), contractility, and the Ca 2+ transients of rat cardiomyocytes, were investigated via patch‐clamp technique and the Ion Optix system. The 6‐Gin decreased the I Ca‐L of normal and ischemic ventricular myocytes by 58.17 ± 1.05% and 55.22 ± 1.34%, respectively. 6‐Gin decreased I Ca‐L in a concentration‐dependent manner with a half‐maximal inhibitory concentration (IC 50 ) 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 Ca 2+ via the inhibition of I Ca‐L and contractility in rat cardiomyocytes.

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