Mangiferin activates the nuclear factor erythroid 2‐related factor pathway to protect SOD1‐G93A induced NSC‐34 motor neurons from oxidative stress and apoptosis

Abstract One of the main factors in the pathophysiology of amyotrophic lateral sclerosis is oxidative stress. Mangiferin (MF), a natural plant polyphenol, has anti‐inflammatory and antioxidant effects. The aim of our study was to investigate the protective effects and mechanisms of MF in the hSOD1‐G93A ALS cell model. Our result revealed that MF treatment reduced the generation of reactive oxygen species (ROS) and malondialdehyde (MDA), decreased oxidative damage, and reduced apoptosis. Additionally, it was observed that MF significantly increased the synthesis of the antioxidant genes hemeoxygenase‐1 and NAD(P)H: quinone oxidoreductase 1, which are downstream of the Nrf2 signaling pathway, and increased the expression and activation of nuclear factor erythroid 2‐related factor 2 (Nrf2). Nrf2 knockdown greatly promoted apoptosis, which was reversed by MF treatment. To summarize, MF promoted the Nrf2 pathway and scavenged MDA and ROS to protect the ALS cell model.