The changes of serum zinc, copper, and selenium levels in epileptic patients: a systematic review and meta-analysis.

INTRODUCTION: It is widely accepted that trace elements have been implicated in various metabolic processes. Valproic acid (VPA) is a remarkably safe and effective antiepileptic drug. There is no consensus option regarding the fluctuations in serum zinc (Zn), copper (Cu), and selenium (Se) in epileptic patients treated with VPA. We applied a meta-analysis to systematically assess the effects of VPA on serum ions in these patients. AREAS COVERED: In this study, we performed a meta-analysis of the changes in serum Zn, Cu, and Se levels in human samples of healthy controls, epileptic patients, and patients treated with VPA. Twenty-two published analyzable studies were selected by searching the databases of PubMed, China National Knowledge Infrastructure (CNKI), Google Scholar, Web of Science, EMBASE, WAN FANG and Vip. EXPERT OPINION: Serum Se levels in epileptic patients were decreased compared to healthy controls. Serum Zn levels in patients with VPA treatment were significantly lower than those in epileptic patients. The results of this meta-analysis are instructive for the intake of trace elements such as Zn, Cu, and Se in the diet balance of patients with epilepsy treated with VPA. Meanwhile, this study provides a theoretical basis for the combined use of other drugs that affect the intake and absorption of trace elements and VPA.

Astragaloside IV Inhibits Membrane Ca[Formula: see text] Current but Enhances Sarcoplasmic Reticulum Ca[Formula: see text] Release.

Astragaloside IV (AS-IV) is one of the active ingredients in Astragalus membrananceus (Huangqi), a traditional Chinese medicine. The present study investigated the effects of AS-IV on Ca[Formula: see text] handling in cardiac myocytes to elucidate its possible mechanism in the treatment of cardiac disease. The results showed that AS-IV at 1 and 10[Formula: see text][Formula: see text]M reduced KCl-induced [Ca[Formula: see text]]i increase ([Formula: see text] from 1.33[Formula: see text][Formula: see text][Formula: see text]0.04 (control, [Formula: see text] 28) to 1.22[Formula: see text][Formula: see text][Formula: see text]0.02 ([Formula: see text], [Formula: see text] 29) and 1.22[Formula: see text][Formula: see text][Formula: see text]0.02 ([Formula: see text] 0.01, [Formula: see text]), but it enhanced Ca[Formula: see text] release from SR ([Formula: see text] from 1.04[Formula: see text][Formula: see text][Formula: see text]0.01 (control, [Formula: see text]) to 1.44[Formula: see text][Formula: see text][Formula: see text]0.03 ([Formula: see text], [Formula: see text]) and 1.60[Formula: see text][Formula: see text][Formula: see text]0.04 ([Formula: see text] 0.01, [Formula: see text]0), in H9c2 cells. Similar results were obtained in native cardiomyocytes. AS-IV at 1 and 10[Formula: see text][Formula: see text]M inhibited L-type Ca[Formula: see text] current ([Formula: see text] from [Formula: see text]4.42[Formula: see text][Formula: see text][Formula: see text]0.58 pA/pF of control to [Formula: see text]2.25[Formula: see text][Formula: see text][Formula: see text]0.12 pA/pF ([Formula: see text] 0.01, [Formula: see text] 5) and [Formula: see text]1.78[Formula: see text][Formula: see text][Formula: see text]0.28 pA/pF ([Formula: see text] 0.01, [Formula: see text] 5) respectively, when the interference of [Ca[Formula: see text]]i was eliminated due to the depletion of SR Ca[Formula: see text] store by thapsigargin, an inhibitor of Ca[Formula: see text] ATPase. Moreover, when BAPTA, a rapid Ca[Formula: see text] chelator, was used, CDI (Ca[Formula: see text]-dependent inactivation) of [Formula: see text] was eliminated, and the inhibitory effects of AS-IV on ICaL were significantly reduced at the same time. These results suggest that AS-IV affects Ca[Formula: see text] homeostasis through two opposite pathways: inhibition of Ca[Formula: see text] influx through L-type Ca[Formula: see text] channel, and promotion of Ca[Formula: see text] release from SR.

Electrophysiological effect and the gating mechanism of astragaloside IV on L-type Ca(2+) channels of guinea-pig ventricular myocytes.

Astragaloside IV (AS-IV) is one of the main active ingredients of Astragalus membranaceus. This study is aimed to investigate AS-IV׳s effects on Ca(2+) channel activity of single cardiomyocytes and single Ca(2+) channels. Whole-cell Ca(2+) currents in freshly dissociated cardiomyocytes were measured using the whole-cell patch-clamp technique. Single Ca(2+) channel currents were examined in cell-attached patches and inside-out patches. In the whole-cell recording, AS-IV reduced the amplitude of L-type Ca(2+) currents (ICaL) in a concentration-dependent manner. Although AS-IV did not alter the steady-state activation curves, the voltage dependence of the current inactivation curves was negatively shifted by AS-IV in a concentration dependent manner. Consistent with the results of the whole-cell recording, in the inside-out configuration the ensemble average of single Ba(2+) current via L-type Ca(2+) channel was dose-dependently reduced by AS-IV. The reduction of unitary Ba(2+) current at 0.1 or 1 µM AS-IV was accounted for a decrease in the channel activity (NPo). In addition to the decrease in NPo, there was a reduction of Po without a change in channel number or an apparent change in single channel current. Furthermore, we found that the open-closed kinetics of the channel were affected by AS-IV. AS-IV induced the shift of L-type Ca(2+) channels from either brief openings (mode 1) or long-lasting openings (mode 2) to no active opening (mode 0). Our results suggest that AS-IV blocks the currents through Ca(2+) channels in guinea-pig ventricular myocytes by affecting the open-closed kinetics of L-type Ca(2+) channels to inhibit the channel activities. This study could provide theoretical basis for the drug exploiting of the monomer of Astragalus membranaceus.