Matrine Inhibits Pacing Induced Atrial Fibrillation by Modulating I_KM3 and I_Ca-L

Abstract

Aim: To elucidate the protective effects of Matrine on atrial fibrillation (AF) induced by electric pacing in mice and underlying molecular and ion channel mechanisms.Methods: AF was introduced by electric pacing in mice and the incidence and duration of AF were evaluated. Functional expression of M3 receptor (M3-R) and Cav1.2 were explored by western and Real-time PCR, action potential (AP) and the density of (IKM3) L-type calcium channel (ICa-L) were both recorded using whole-cell patch in isolated atrial cardiomyocytes.Results: In control group, incidence and duration of AF induced by electric pacing were 50 ± 17% and 3.68 ± 1.84 s, respectively; after application of carbachol 50 µg/kg both incidence and duration of AF were significantly increased to 86 ± 24% and 65.2 ± 29.0 s. Compared with control group, pretreatment of Matrine for 15 days significantly reduced AF incidence and duration in dose-dependent manner. Atrial membrane-protein expression of M3-R was decreased and membrane Cav1.2 expression was up-regulated. In single Matrine-treated atrial cardiomyocyte the density of IKM3 was significantly decreased by 39% as well compared with control group, P < 0.05, whereas, ICa-L density of atrium was increased by 40%.Conclusion: These data demonstrated at the first time that the anti-AF effects of Matrine may due, at least in part, to down-regulation of IKM3 density and M3-R expression and up-regulation of ICa-L density and α1C/Cav1.2 expression.

Matrine improved the function of heart failure in rats via inhibiting apoptosis and blocking β3-adrenoreceptor/endothelial nitric oxide synthase pathway

“…Numerous studies have demonstrated that matrine possesses numerous biological activities, including antitumor, antivirus, antioxidant and anti-inflammatory actions (3,(6)(7)(8)12). However, the effects of matrine on heart failure have not previously been elucidated.…”

“…In one study, matrine triggered the apoptosis of cardiac fibroblasts and thereby inhibited Ang II-induced hyperplasic growth via the regulation of Bcl-2/Bax expression and caspase-3 activation (11). Atrial fibrillation was also prevented by matrine through the downregulation of I KM3 density and upregulation of ICa-L density (12). In addition, matrine produced a positive inotropic effect on rat hearts through enhancing the calcium influx (13).…”

Matrine Inhibits Mouse Sperm Function by Reducing Sperm [Ca2+]i and Phospho-ERK1/2

“…2B), were inhibited by matrine, implying that matrine may affect sperm Ca 2+ signaling. In fact, there were reports showing that matrine could alter [Ca 2+ ] i in ventricular myocytes [12,13]. Therefore, we used a single sperm [Ca 2+ ] i imaging assay to determine whether matrine affects mouse sperm [Ca 2+ ] i .…”

“…Matrine has been widely used for the treatment of chronic hepatitis B and chronic hepatitis C since 1998 and has recently been reported to have anti-tumor activities with potential as an adjunct therapy for cancers [5,7,8,9,10,11]. Based on its effects on potassium and calcium currents as well as intracellular calcium concentration ([Ca 2+ ] i ) in rat ventricular myocytes and mouse atrial cardiomyocytes, matrine has also been used for the treatment of heart arrhythmias [12,13,14]. Clearly, matrine is a research focus in Chinese medicine.…”

Oxymatrine inhibits proliferation of human bladder cancer T24 cells by inducing apoptosis and cell cycle arrest

“…Matrine may transform into oxymatrine, which may also be extracted from Sophora flavecens, and the nitrogen-oxygen bond may split under certain conditions transforming oxymatrine back to matrine (7). Several studies have demonstrated the multiple beneficial effects of matrine, including anti-arrhythmia (8), anti-inflammation (9,10) and anti-fibrosis (11,12) effects, with minimal side effects reported. In addition, previous studies have shown that matrine induces apoptosis in several cancer cell lines, including breast cancer MCF-7 cells (13) and pancreatic cancer PANC1 cells (14), using various mechanisms, which potentiate the role of matrine in cancer therapy.…”