Emodin is a natural anthraquinone derivative with numerous beneficial effects, including antioxidant properties, anti-tumor activities, and protecting the nerves. Zinc-induced neurotoxicity plays a crucial role in the pathogenesis of vascular dementia (VD) and Parkinson's disease (PD). Here, the protective activity of emodin inhibiting zinc-induced neurotoxicity and its molecular mechanisms such as cellular Zn2+ influx and zinc-induced gene expression were examined using human neuroblastoma cells (SH-SY5Y cells). Our findings showed that emodin obviously enhanced cell viability and reduced cell apoptosis and lactate dehydrogenase release. Bedsides, we detected a decrease of intracellular Zn2+ concentration after SH-SY5Y cells were pretreated with emodin. Simultaneously, the expression of zinc transporter-1, metallothionein-1, and metallothionein-2 were weakened in emodin-pretreated SH-SY5Y cells. In addition, emodin prevented the depletion of NAD+ and ATP induced by zinc. Emodin also reduced intracellular reactive oxygen species and endoplasmic reticulum-stress levels. Strikingly, emodin elevated SH-SY5Y cell viability and inhibited cell apoptosis caused by AMP-activated protein kinase signaling pathway activation. Thus, emodin could protect against neurotoxicity induced by Zn2+ in neuroblastoma SH-SY5Y cells. It is expected to have future therapeutic potential for VD or PD and other neurodegenerative diseases.
Keywords: AMPK; ER-stress; Emodin; Zinc; senile dementia.
© 2019 The Author(s).