Protective role of silibinin against myocardial ischemia/reperfusion injury-induced cardiac dysfunction.

Silibinin is a traditional medicine and utilized for liver protection with antioxidant, anti-inflammation and anti-apoptosis properties. However, its role in myocardial I/R injury and the mechanism involved is currently unknown. In the present study, Silibinin treatment improves cardiac function and limits infarct size, and subsequently inhibits fibrotic remodeling in mice with myocardial I/R injury. Mechanistically, silibinin reduces cardiomyocytes apoptosis, attenuates mitochondrial impairment and endoplasmic reticulum (ER) stress, alleviates ROS generation, neutrophil infiltration and cytokines release. Consistently, silibinin prevents H9C2 cells from hypoxia/reperfusion-induced cell death, oxidative stress and inflammation in vitro. Furthermore, H9C2 cells treated with silibinin blocks NF-κB signaling activation by inhibiting IKKα phosphorylation, IκBα degradation and p65 NF-κB nuclear translocation during hypoxia/ reperfusion. In addition, silibinin plus BAY 11-7082 (a selected NF-κB inhibitor) do not provide incremental benefits in improving myocytes apoptosis, oxidative stress and inflammation in comparison with NF-κB signaling inhibition only. Thus, silibinin-mediated cardioprotection in myocardial I/R injury is associated with decreased apoptosis, oxidative stress and inflammatory response through deactivation of NF-κB pathway.

Antiarrhythmic effects and potential mechanism of WenXin KeLi in cardiac Purkinje cells.

BACKGROUND: Previous studies have demonstrated that WenXin KeLi (WXKL), a traditional Chinese medicine, can exert antiarrhythmic properties through complex multichannel inhibition, but its pharmacologic effect remains to be elucidated, especially in the cardiac conductive system. OBJECTIVE: To explore the antiarrhythmic property of WXKL in cardiac Purkinje cells (PCs). METHODS: PCs were isolated from rabbit hearts and action potentials (APs) and ion currents were recorded by whole-cell patch clamp technique. Anemonia toxin II (ATX-II) and isoproterenol (ISO) were used to induce early or delayed afterdepolarizations (EADs, DADs) or triggered activities (TAs). RESULTS: WXKL (1 g/L and 5 g/L) significantly abbreviated the action potential duration (APD) of PCs in a dose- and rate-dependent manner. Treatment of PCs with ATX-II (2 nM) prolonged APD and induced EADs, which were significantly suppressed by WXKL. WXKL (1, 5 g/L) also inhibited ISO-induced EADs, DADs, and TAs. To reveal the ionic mechanisms, we studied the effects of WXKL on late sodium current (I(NaL)), peak sodium current (I(NaP)), and L-type calcium currents (ICaL) in PCs. WXKL-attenuated ATX-II (5 nM) induced I(NaL) augmentation and blocked I(NaL) with an IC50 of 4.3 ± 0.5 g/L, which is 3- to 4-fold more selective than that of I(NaP) (13.3 ± 0.9 g/L) and ICaL (17.6 ± 1.4 g/L). Moreover, WXKL exerted significantly less use-dependent block of I(NaP) than that of flecainide, indicating its lower proarrhythmic effect. CONCLUSIONS: WXKL exhibits antiarrhythmic properties in cardiac PCs via selective inhibition of I(NaL).