Vinpocetine and Vasoactive Intestinal Peptide Attenuate Manganese-Induced Toxicity in NE-4C Cells

Increased concentration of manganese (Mn) in the brain is known to be associated with excitotoxicity and neuroinflammation. Vinpocetine, an alkaloid derived from the plant Vinca minor L., basically shows its effect via phosphodiesterase inhibition and voltage-dependent Na+ channels. Vasoactive intestinal peptide (VIP) has gastrointestinal, vasomotor, muscular, and neuroprotective effects. The aim of this study was to examine the potential protective effects of vinpocetine and VIP against Mn toxicity in NE-4C neural stem cells (NSCs). VIP treatment at 1 μM and vinpocetine treatment at 2 μM concentrations were sufficient to yield maximum protection, and these concentrations were adopted in the following experiments. In this study, Mn treatment significantly increased lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) production, and triggered cell death in NE-4C cultures. However, significant reduction in LDH release was observed following vinpocetine or VIP treatments when compared with control. Similar to these findings, vinpocetine or VIP treatments significantly reduced membrane degradation induced by Mn (p