Inhibitory Effects of Nobiletin on Voltage-Gated Na+ Channel in Rat Ventricular Myocytes Based on Electrophysiological Analysis and Molecular Docking Method.

Nobiletin (NOB) has attracted much attention owing to its outstanding bioactivities. This study aimed to investigate its anti-arrhythmic effect through electrophysiological and molecular docking studies. We assessed the anti-arrhythmic effects of NOB using aconitine-induced ventricular arrhythmia in a rat model and the electrophysiological effects of NOB on rat cardiomyocytes utilizing whole-cell patch-clamp techniques. Moreover, we investigated the binding characters of NOB with rNav1.5, rNav1.5/QQQ, and hNaV1.5 via docking analysis, comparing them with amiodarone and aconitine. NOB pretreatment delayed susceptibility to ventricular premature and ventricular tachycardia and decreased the incidence of fatal ventricular fibrillation. Whole-cell patch-clamp assays demonstrated that the peak current density of the voltage-gated Na+ channel current was reversibly reduced by NOB in a concentration-dependent manner. The steady-state activation and recovery curves were shifted in the positive direction along the voltage axis, and the steady-state inactivation curve was shifted in the negative direction along the voltage axis, as shown by gating kinetics. The molecular docking study showed NOB formed a π-π stacking interaction with rNav1.5 and rNav1.5/QQQ upon Phe-1762, which is the homolog to Phe-1760 in hNaV1.5 and plays an important role in antiarrhythmic action This study reveals that NOB may act as a class I sodium channel anti-arrhythmia agent.

Inhibitory effects of aloperine on voltage-gated Na+ channels in rat ventricular myocytes.

Aloperine (ALO), a quinolizidine alkaloid extracted from Sophora alopecuroides L., modulates hypertension, ventricular remodeling, and myocardial ischemia. However, few studies have evaluated the effects of ALO on other cardiovascular parameters. Accordingly, in this study, we used a rat model of aconitine-induced ventricular arrhythmia to assess the effects of ALO. Notably, ALO pretreatment delayed the onset of ventricular premature and ventricular tachycardia and reduced the incidence of fatal ventricular fibrillation. Moreover, whole-cell patch-clamp assays in rats' ventricular myocyte showed that ALO (3, 10, and 30 µM) significantly reduced the peak sodium current density of voltage-gated Na+ channel currents (INa) in a concentration-dependent manner. The gating kinetics characteristics showed that the steady-state activation and recovery curve were shifted in positive direction along the voltage axis, respectively, and the steady-state inactivation curve was shifted in negative direction along the voltage axis, i.e., which was similar to the inhibitory effects of amiodarone. These results indicated that ALO had anti-arrhythmic effects, partly attributed to INa inhibition. ALO may act as a class I sodium channel anti-arrhythmia agent.

Cavitation inception of water with solid nanoparticles: A molecular dynamics study.

Cavitation in liquid with impurities is important in heterogeneous nucleation applications. One of the most widely existing kinds of impurities is solid particles, which can be found in natural water from rivers and specially prepared water such as nanofluids. Understanding the effects caused by the existence of nanoparticles on cavitation in water is vital to the rapidly developed nanotechnologies and medical researches. In this study, cavitation in water with nanoparticles is investigated through molecular dynamics simulations. The effects by nanoparticle materials and sizes on cavitation are discussed by using SiO2 and polyethylene spherical nanoparticles with different diameters. The nucleation rate and the formation of critical bubbles in cavitation are studied via the Voronoi tessellation and the mean first passage time methods. The hydrogen bond network in water is also analyzed. Results reveal that SiO⁠2 and polyethylene nanoparticles may destabilize the hydrogen bond network in water. With the same particle size, cavitation in water with polyethylene nanoparticles is promoted to a greater extent than that with SiO2 nanoparticles. With the same nanoparticle material, cavitation is promoted with the increase in particle size in a range spanning half to ten times the critical bubble radius. Beyond this range, particle size has little influence on cavitation. Reasons for those effects on cavitation due to the presence of solid nanoparticles are discussed by analysing the changes of hydrogen bonds network in water.