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

Abstract

Background: Matrine is a bioactive alkaloid that has a variety of pharmacological effects and is widely used in Chinese medicine. However, its effects on male reproduction are not well known. In this study, we aimed to investigate the in vitro toxicity of matrine on mature mouse sperm. Methods: Mouse cauda epididymal sperm were exposed to matrine (10-200 µM) in vitro. The viability, motility, capacitation, acrosome reaction and fertilization ability of the mouse sperm were examined. Furthermore, the intracellular calcium concentration ([Ca²⁺]_i), calcium (Catsper) and potassium (Ksper) currents, and phosphorylation of extracellular signal regulated kinases 1/2 (p-ERK1/2) of the sperm were analyzed. Results: After exposure to 100 µM or more of matrine, mouse cauda epididymal sperm exhibited a significant reduction in total motility, progressive motility, linear velocity and acrosome reaction rate induced by Ca²⁺ ionophore A23187. As a result, the fertilization ability of mouse sperm was remarkably decreased by matrine. Our data further demonstrated that matrine significantly reduced sperm [Ca²⁺]_i and [Ca²⁺]_i-related p-ERK1/2; however, both the CatSper and KSper currents, which are thought to interactively regulate Ca²⁺ influx in sperm, were not affected by matrine. Conclusion: Our findings indicate that matrine inhibits mouse sperm function by reducing sperm [Ca²⁺]_i and suppressing the phosphorylation of ERK1/2.

A Systematic Review of the Pharmacology, Toxicology and Pharmacokinetics of Matrine

“…Further studies are needed on the mechanism involved. In addition, as summarized in Tables 1 and 2, the toxic doses of MT significantly affected the mitochondrial apoptotic pathway, Nrf2 pathway and In vivo (Luo et al, 2015;Luo et al 2016) FIGURE 3 | Toxicity and mechanism of Matrine. Zhang et al, 2008 Rat Oral MT, 40 mg/kg C max and T max of approximately 3900 ng/ml and 50 min, respectively Wu et al, 2003 Rat Intravenous MT, 15 mg/kg Rapidly distributed to various tissues and organs, such as liver, spleen and kidney.…”

“…Investigation of the relationship between MTinduced neurotoxicity and oxidative stress in PC12 cells indicated that MT induced high level of oxidative stress after treatment with graded concentrations of MT (2-8 mM) for 48 h, resulting in a reduction of SOD and an increase in ROS and MDA, as well as activation of the mitochondria-dependent apoptotic pathway (Shen et al, 2017). In terms of reproductive toxicity, Luo et al (2015) was the first to show that MT (100-200 µM) suppressed mouse sperm function by reducing sperm [Ca 2+ ] i and inhibiting the phosphorylation of ERK1/2. Moreover, further studies indicated that MT (10 ang50 mg/kg/day for 30 days) inhibited mouse sperm function through the [Ca 2+ ] i -related mechanism via the CatSper channel, which is the main channel for controlling extracellular Ca 2+ influx in mouse sperm (Luo et al, 2015;Luo et al, 2016).…”

Sphingomyelin Synthase 2 Participate in the Regulation of Sperm Motility and Apoptosis

“…The normal semen samples were treated with the anti-SMS2 antibody in a 5% CO 2 incubator for 1 h at 37 °C, and the control groups were treated with the IgG antibody. For each group, more than 200 sperm cells were counted [ 43 ]. Then, these treated cells were used to measure the motility and penetration into methylcellulose.…”

Construction of Multiple Switchable Sensors and Logic Gates Based on Carboxylated Multi-Walled Carbon Nanotubes/Poly(N,N-Diethylacrylamide)

“…Matrine and sophoridine are quinolizidine alkaloids isolated from traditional Chinese medicine such as Sophora flavescens, Sophora subprostrata, or Sophora alopecuroides, which are tetracyclic quinolizine compounds with a molecular skeleton and can be regarded as a combination of two quinolizine rings [ 19 , 20 ]. In recent years, it has been discovered that the alkaloids of S. flavescens exhibit anti-arrhythmic, anti-inflammatory, anti-fibrosis, anti-tumor, and numerous other significant pharmacological activities, and various formulations have been widely used in clinical practice [ 21 , 22 , 23 , 24 ]. Therefore, in the present work, we used matrine and sophoridine as target drug molecule probes to study the switching properties of the binary carboxylated multi-walled carbon nanotubes/poly( N , N -diethylacrylamide) (c-MWCNTs/PDEA) film system.…”