Neuroprotective effects of Lycium barbarum polysaccharide on light-induced oxidative stress and mitochondrial damage via the Nrf2/HO-1 pathway in mouse hippocampal neurons

Light at night (LAN) induced cognitive impairment associated with oxidative stress in mice has been reported. Lycium barbarum polysaccharide (LBP) exhibits anti-tumor, anti-oxidant and neuroprotective effects, yet the neuroprotective effect on light-induced neuron damage still unclear. Here, mice exposed to LAN displayed cognitive impairment and depressive like behavior, which was reversed by LBP treatment. Meanwhile, LBP alleviated light-induced higher apoptosis and mitochondrial damage in HT-22 cells. Also, LBP prevented the decreased of mitochondrial membrane permeabilization (MMP) level in light-treated cells. Additionally, LBP demonstrated its antioxidant potential by reducing ROS production and malondialdehyde (MDA) level, while simultaneously enhancing the levels of superoxide dismutase (SOD) and glutathione peroxidases (GSH-Px) in both light-treated mice and HT-22 cells. Furthermore, the mRNA and protein expression of Nrf2 (NF-E2-related factor 2), heme oxygenease-1 (HO-1), and NAD(P)H quinone oxidoreductase (NQO1) were decreased in both light-treated mice and cells. Additionally, LBP treatment reversed light-induced the inhibition of Nrf2/HO-1 signaling pathway in both mice and cells. Moreover, Nrf2 antagonist ML385 significantly eliminated the neuroprotection of LBP on cell apoptosis, oxidative stress and mitochondrial damage in light-treated cells. These results indicate that LBP can rescue light-induced neurotoxicity in mice and HT-22 cells by activating the Nrf2/HO-1 signaling pathway.