Neuroprotective Effect of Gallocatechin Gallate on Glutamate-Induced Oxidative Stress in Hippocampal HT22 Cells

Abstract

Oxidative stress leads to protein degeneration or mitochondrial dysfunction, causing neuronal cell death. Glutamate is a neurotransmitter that nerve cells use to send signals. However, the excess accumulation of glutamate can cause excitotoxicity in the central nervous system. In this study, we deciphered the molecular mechanism of catechin-mediated neuroprotective effect on glutamate-induced oxidative stress in mouse hippocampal neuronal HT22 cells. Cellular antioxidant activity was determined using the 1,1-diphenyl-picryl hydrazyl (DPPH) assay and 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) staining. Furthermore, the levels of intracellular calcium (Ca2+) as well as nuclear condensation and protein expression related to neuronal damage were assessed. All five catechins (epigallocatechin gallate, gallocatechin gallate (GCG), gallocatechin, epicatechin gallate, and epicatechin) showed strong antioxidant effects. Among them, GCG exhibited the highest neuroprotective effect against glutamate excitotoxicity and was used for further mechanistic studies. The glutamate-induced increase in intracellular Ca2+ was reduced after GCG treatment. Moreover, GCG reduced nuclear condensation and the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinases (JNK) involved in cell death. The neuroprotective effect of GCG against glutamate-induced oxidative stress in HT22 cells was attributed to the reduction in intracellular free radicals and Ca2+ influx and also the inhibition of phosphorylation of ERK and JNK. Furthermore, the antioxidant effect of GCG was found to be likely due to the inhibition of phosphorylation of ERK and JNK that led to the effective suppression of neurocytotoxicity caused by glutamate in HT22 cells.

Protective Effect of NGR1 against Glutamate-Induced Cytotoxicity in HT22 Hippocampal Neuronal Cells by Upregulating the SIRT1/Wnt/β-Catenin Pathway

“…The oxidative stress induced by glutamate will trigger the changes in the structure and function of the neurons and cause the death of neurons [ 14 , 24 ]. Earlier studies showed that plant extracts and compounds with strong antioxidant activity protected glutamate-induced neuronal death [ 4 , 25 ]. In the current study, we used mouse-derived hippocampal HT22 cells to study the neuroprotective effect of NGR1 against glutamate-induced cell apoptosis and to explore the neuroprotective mechanism of action.…”

“…Mitochondrial dysfunction has an integral role in the development of oxidative stress and leads to increased oxidative stress, while the ultrastructure of mitochondria is destroyed, which further exacerbates mitochondrial dysfunction [ 28 ]. Plant extracts with antioxidant activity can inhibit glutamate-induced mitochondrial dysfunction and increase in Ca 2+ concentration in HT22 cells [ 25 ]. In this study, we found that NGR1 has an effect on mitochondrial dysfunction and Ca 2+ concentration.…”

Targeting Oxidative Stress and Inflammation in Intervertebral Disc Degeneration: Therapeutic Perspectives of Phytochemicals

“…(-)-Epigallocatechin-3-gallate (EGCG) is a polyphenol that is abundantly found in tea ( Butt et al, 2015 ). EGCG shows a variety of functions in many diseases, such as antiarteriosclerosis ( Liu S. et al, 2017 ), antioxidant ( Park et al, 2021 ), antibacterial ( Noor Mohammadi et al, 2019 ), anti-inflammatory ( Ma et al, 2021 ), and anti-tumor activities ( Farabegoli and Pinheiro, 2022 ). The flow cytometry results of the study ( Tian et al, 2020 ) conducted by Tian et al showed that EGCG could inhibit the apoptosis and cell cycle arrest induced by H 2 O 2 .…”

Antioxidant Activity of Urtica dioica: An Important Property Contributing to Multiple Biological Activities

“…UDLS was found to be an effective antioxidant that may be helpful in recovery from brain injury. It could be developed as an antiapoptotic supplement, promoting cell survival in the brain [ 69 , 70 ].…”