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Mangiferin Ameliorates Glutamate-Induced Excitatory Toxicity in SH-SY5Y Cells via Nrf2/HO-1 and Apoptosis Pathway
Ruiyuan Zhou1, Yanan Gao1, Bo Shang1
1Key Laboratory of Resource Biology and Biotechnology in Western China (Northwest University), Ministry of Education, Xi'an, Shaanxi Province, PR China.
Abstract:
Mangiferin (Mng) is a polyphenolic natural flavanthrone known for antioxidant, antiviral, immunomodulatory, and antibacterial properties. In center nervous system, excessive Glutamate (Glu) can lead to oxidative stress by elevating ROS generation and subsequently undermining the antioxidant defense system, resulting neuron injury so far as to death and different neurological disorders. The study aimed to assess the suppressive capability of Mng on Glu-induced oxidative stress neuron injury in SH-SY5Y cells. Cell viability was detected by CCK-8 after 24-h treatment with Glu and Mng. Mitochondrial membrane depolarization, ROS generation, and occurrence of cell apoptosis were measured by flow cytometry. The detection of Nrf2/HO-1 and apoptosis pathway were performed using Western blot. The finding indicated that Mng has a positive effect on cell viability decline and the imbalance of mitochondrial membrane potential, caused by Glu, while decreasing the levels of ROS and malondialdehyde (MDA). Additionally, it increased the glutathione (GSH) levels and superoxide dismutase (SOD) activity. We also found that Glu stimulation resulted in an elevation of Ca2+ influx, however Mng treatment exhibited the ability to decrease Ca2+ influx through suppressing NR1 and NR2A expression. Mng effectively decreased the generation of ROS and the occurrence of cell apoptosis by upregulating Nrf2/HO-1 pathway and downregulating MAPK and Bax/Bcl-2 pathways. In summary, Mng has the potential to decrease oxidative stress by Nrf2/HO-1 and Bax/Bcl-2 pathways, while inhibiting the apoptosis.
Insights
Mangiferin (Mng) protects neurons from glutamate-induced oxidative stress and apoptosis. This natural compound enhances cell viability and antioxidant defenses, offering potential for neurological disorder treatment.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Excess glutamate (Glu) causes oxidative stress and neuron injury, contributing to neurological disorders.
- Mangiferin (Mng) is a natural flavanthrone with known antioxidant and other beneficial properties.
Purpose of the Study:
- To investigate the protective effects of Mng against Glu-induced oxidative stress and apoptosis in SH-SY5Y neuronal cells.
- To elucidate the molecular mechanisms underlying Mng's neuroprotective actions.
Main Methods:
- Cell viability assays (CCK-8) were used to assess cell survival.
- Flow cytometry measured mitochondrial membrane potential, reactive oxygen species (ROS) generation, and apoptosis.
- Western blot analysis detected key proteins in the Nrf2/HO-1 and apoptosis pathways.
Main Results:
- Mng improved cell viability, restored mitochondrial membrane potential, and reduced ROS and malondialdehyde (MDA) levels induced by Glu.
- Mng increased glutathione (GSH) and superoxide dismutase (SOD) activity, while decreasing Ca2+ influx by suppressing NR1 and NR2A.
- Mng upregulated the Nrf2/HO-1 pathway and downregulated MAPK and Bax/Bcl-2 pathways, thereby reducing apoptosis.
Conclusions:
- Mangiferin demonstrates significant neuroprotective effects against glutamate-induced oxidative stress and apoptosis in neuronal cells.
- Mng exerts its protective effects by modulating the Nrf2/HO-1 and apoptosis-related pathways.
- Mangiferin shows therapeutic potential for neurological conditions associated with oxidative stress and neuronal death.
