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

Int J Biol Macromol. 2023 Nov 1:251:126315. doi: 10.1016/j.ijbiomac.2023.126315. Epub 2023 Aug 14.

Abstract

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.

Keywords: Light at night; Lycium barbarum polysaccharide; Nrf2/HO-1.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Cell Line
  • Drugs, Chinese Herbal* / pharmacology
  • Heme Oxygenase-1 / metabolism
  • Hippocampus* / drug effects
  • Hippocampus* / metabolism
  • Light* / adverse effects
  • Male
  • Membrane Proteins
  • Mice
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • NF-E2-Related Factor 2* / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Neuroprotective Agents* / pharmacology
  • Oxidative Stress* / drug effects
  • Reactive Oxygen Species / metabolism
  • Signal Transduction* / drug effects

Substances

  • Antioxidants
  • Drugs, Chinese Herbal
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • lycium barbarum polysaccharide
  • Membrane Proteins
  • Neuroprotective Agents
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Reactive Oxygen Species