Effects of Gintonin-Enriched Fraction on Methylmercury-Induced Neurotoxicity and Organ Methylmercury Elimination

Abstract

Gintonin is a newly discovered ingredient of ginseng and plays an exogenous ligand for G protein-coupled lysophosphatidic acid receptors. We previously showed that gintonin exhibits diverse effects from neurotransmitter release to improvement of Alzheimer’s disease-related cognitive dysfunctions. However, previous studies did not show whether gintonin has protective effects against environmental heavy metal. We investigated the effects of gintonin-enriched fraction (GEF) on methylmercury (MeHg)-induced neurotoxicity and learning and memory dysfunction and on organ MeHg elimination. Using hippocampal neural progenitor cells (hNPCs) and mice we examined the effects of GEF on MeHg-induced hippocampal NPC neurotoxicity, on formation of reactive oxygen species (ROS), and on in vivo learning and memory functions after acute MeHg exposure. Treatment of GEF to hNPCs attenuated MeHg-induced neurotoxicity with concentration- and time-dependent manner. GEF treatment inhibited MeHg- and ROS inducer-induced ROS formations. Long-term treatment of GEF also improved MeHg-induced learning and memory dysfunctions. Oral administration of GEF decreased the concentrations of MeHg in blood, brain, liver, and kidney. This is the first report that GEF attenuated MeHg-induced in vitro and in vivo neurotoxicities through LPA (lysophosphatidic acids) receptor-independent manner and increased organ MeHg elimination. GEF-mediated neuroprotection might achieve via inhibition of ROS formation and facilitation of MeHg elimination from body.

Ongoing Research on the Role of Gintonin in the Management of Neurodegenerative Disorders

“…Moreover, it was shown that gintonin regulates the expression of VEGF in astrocytes, which might provide protection against hypoxic injury [ 76 ]. It has been suggested that gintonin is able to protect mouse brain against methylmercury-induced neurotoxicity and learning processes [ 77 ]. One of the most common mechanisms, which has been extensively highlighted in a study of gintonin, is its antioxidant effects; a simple diagram is given here ( Figure 8 ).…”

L-Ascorbic Acid 2-Phosphate Attenuates Methylmercury-Induced Apoptosis by Inhibiting Reactive Oxygen Species Accumulation and DNA Damage in Human SH-SY5Y Cells

“…These results are also consistent with another report that 1 μM MeHg induces oxidative stress and subsequent cell death in SH-SY5Y cells [ 22 ]. MeHg was previously shown to increase intracellular ROS [ 16 , 17 ], causing lipid peroxidation and leading to intracellular oxidative stress [ 30 ]. Together, these findings indicate that oxidative stress is one of the main mechanisms of MeHg-induced CNS damage [ 51 ].…”

“…At present, there are several mechanisms of MeHg-induced injury, in which ROS are an important factor [ 14 ]. MeHg can increase intracellular ROS [ 15 , 16 ] and cause lipid peroxidation, which leads to oxidative stress in cells [ 17 ] and exerts toxic effects [ 18 ]. Therefore, the activation of antioxidant mechanisms prevents MeHg poisoning [ 19 ].…”

Evaluation of Blood-Brain-Barrier Permeability, Neurotoxicity, and Potential Cognitive Impairment by Pseudomonas aeruginosa’s Virulence Factor Pyocyanin

“…The study found PCN to be affecting the locomotor activity of the subjects as well as their immobility behavior. PCN has also been used to induced ROS in human neural progenitor cells (hNPCs), mediated its oxidative stress levels using gintonin-enriched fraction [ 32 ].…”