Lycium ruthenicum anthocyanins alleviate acrylamide-induced neurotoxicity in SH-SY5Y cells by mitigating ferroptosis via the Nrf2/GPX4 signaling pathway

Acrylamide (ACR), known for its neurotoxic properties, might be linked to oxidative stress and ferroptosis. Lycium ruthenicum anthocyanins (LRA) are known for their antioxidant and neuroprotective properties. This research aimed to explore LRA's defensive role against ACR-induced neurotoxicity in SH-SY5Y cells and to understand the fundamental processes. To develop a neurotoxicity model, SH-SY5Y cells were exposed to ACR, and their survival was subsequently assessed using the CCK-8 assay. The levels of ROS, MDA, GSH, SOD, and Fe(II) in cells were measured with the corresponding assay kits. The concentrations of Nrf2, NQO1, HO-1, GPX4, xCT, TFR1, DMT1, FPN, FTH1, and FTL within cell were determined using Western blotting. LRA improved cell survival, increased the internal concentrations of GSH and SOD, and decreased ROS, MDA, and Fe(II) levels. Significantly, LRA reduced the expression levels of TFR1 and DMT1, simultaneously increasing the expression of Nrf2, NQO1, HO-1, GPX4, xCT, FPN, FTH1, and FTL. After silencing of the Nrf2/GPX4 genes, the regulatory effect of LRA on the Nrf2 pathway and GPX4 factor was diminished. LRA mitigates oxidative stress and ferroptosis through the activation of the Nrf2/GPX4 pathway, thus reducing ACR-induced neurotoxicity. LRA shows promise as a neuroprotective agent against neurotoxicity caused by ACR. • Acrylamide induces ferroptosis through lipid peroxidation, leading to neurotoxicity in SH-SY5Y cells. • Lycium ruthenicum anthocyanins act as neuroprotective agents against acrylamide neurotoxicity. • Lycium ruthenicum anthocyanins activate the Nrf2/GPX4 pathway and protects SH-SY5Y cells from oxidative stress.