Pseudoginsenoside-F11 attenuates cognitive impairment by ameliorating oxidative stress and neuroinflammation in d‑galactose-treated mice.

Abstract

Oxidative stress and neuroinflammation are thought to be the two key early events during the process of mild cognitive impairment (MCI). Therefore, effective regulation of oxidative stress and neuroinflammation is an important aspect of preventing and improving MCI. We previously found that pseudoginsenoside-F11 (PF11), an ocotillol-type saponin, markedly reduced cognitive impairment in APP/PS1 mice and oAβ1-42-injected mice. In the present study, we further evaluate the effect of PF11 on learning and memory dysfunction in d‑galactose (d‑gal)-treated mice model of MCI. C57BL/6 mice received daily subcutaneous injections of d‑gal (100 mg/kg) and oral administration of PF11 (2, 4, 8, 16 mg/kg) for 9 weeks. We observed that PF11 significantly alleviated d‑gal-induced cognitive impairment, attenuated the loss of neuron and the over-activation of microglia in hippocampus of d‑gal-treated mice. The elevated levels of nod-like receptor protein 3 (NLRP3) inflammasome in hippocampus of d‑gal-treated mice were reduced by PF11 through reducing the accumulation of advanced glycation endproducts (AGEs) and the expression of the receptor of advanced glycation endproducts (RAGE). Moreover, PF11 significantly decreased H2O2 and malondialdehyde (MDA) levels, improved superoxide dismutase (SOD) activity and increased glutathione (GSH) level in d‑gal-treated mice. Finally, d‑gal treatment reduced the level of nuclear factor erythroid-related factor 2 (Nrf2) and glutathione S-transferase (GST) in hippocampus, which could reverse by PF11. Together, our findings indicated that PF11 exerts a protective effect against MCI-like pathological changes.

• Authors: Zhen Zhang, Hanlin Yang, Jingyu Yang, Jun Xie, Jiaoyan Xu, Chen Liu, Chunfu Wu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 67 Pg. 78-86 (Feb 2019) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 30537634 (Publication Type: Journal Article)
• Copyright: Copyright © 2018. Published by Elsevier B.V.

Chemical References

• Antioxidants
• Ginsenosides
• NF-E2-Related Factor 2
• Nfe2l2 protein, mouse
• pseudoginsenoside F11
• Hydrogen Peroxide
• Galactose

Topics

• Animals
• Antioxidants (therapeutic use)
• Cells, Cultured
• Cognitive Dysfunction (drug therapy)
• Disease Models, Animal
• Galactose (administration & dosage)
• Ginsenosides (therapeutic use)
• Hippocampus (pathology)
• Humans
• Hydrogen Peroxide (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Microglia (drug effects, physiology)
• NF-E2-Related Factor 2 (metabolism)
• Neurogenic Inflammation (drug therapy)
• Neurons (drug effects, physiology)
• Oxidative Stress (drug effects)