Mangiferin Ameliorates Glutamate‐Induced Excitatory Toxicity in SH‐SY5Y Cells via Nrf2/HO‐1 and Apoptosis Pathway

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.