Polysaccharide from Paris polyphylla improves learning and memory ability in D-galactose-induced aging model mice based on antioxidation, p19/p53/p21, and Wnt/β-catenin signaling pathways

Int J Biol Macromol. 2023 Nov 1:251:126311. doi: 10.1016/j.ijbiomac.2023.126311. Epub 2023 Aug 12.

Abstract

The current study aimed to investigate the effects and mechanisms of Paris polyphylla polysaccharide component 1 (PPPm-1) to improve learning and memory in D-galactose-induced aging model mice. We determined the effects of PPPm-1 on the brain, organ index, and behavior in the aging model mice induced by D-galactose to study learning and memory improvement. UV-Vis spectrophotometry helped determine the PPPm-1 effect on antioxidant parameters associated with learning and memory in the brain and related organs of aging mice. Moreover, in the hippocampi of aging model mice, PPPm-1 effect on the mRNA and protein expressions of p19, p53, p21, P16, Rb, Wnt/1, β-catenin, CyclinD1, TCF-4, and GSK-3β were detected using the quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The results indicated that PPPm-1 could increase the brain and organ indexes, the avoidance latency, the total distance and average speed in the water maze, and the SOD and GSH-PX activities in the brain, liver tissues, and plasma. Moreover, the mRNA and protein expressions of Wnt/1, β-catenin, CyclinD1, and TCF-4 were also elevated in the hippocampi of aging model mice. However, the error times in step-through tests, the MDA content in the brain and liver tissues, the AChE activity in the brain tissue, the protein expressions of P16, Rb in the hippocampi, and the mRNA and protein expressions of p19, p53, p21, and GSK-3β in the hippocampi of aging model mice were significantly decreased. Thus, PPPm-1 significantly enhanced the learning and memory impairment induced by D-galactose in mice. The action mechanisms were associated with anti-oxidative stress, cholinergic nervous system function regulation, LTP enhancement in long-term memory, down-regulated expression of p19/p53/p21 signaling pathway factors, and Wnt/β-catenin signaling pathway activation.

Keywords: Antioxidation; Learning and memory; Paris polyphylla polysaccharide; Wnt/β-catenin signaling pathway; p19/p53/p21 signaling pathway.

MeSH terms

  • Aging* / drug effects
  • Animals
  • Antioxidants* / metabolism
  • Antioxidants* / pharmacology
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Disease Models, Animal
  • Galactose*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Learning / drug effects
  • Male
  • Maze Learning / drug effects
  • Memory* / drug effects
  • Mice
  • Polysaccharides* / chemistry
  • Polysaccharides* / pharmacology
  • Tumor Suppressor Protein p53* / genetics
  • Tumor Suppressor Protein p53* / metabolism
  • Wnt Signaling Pathway* / drug effects

Substances

  • Galactose
  • Polysaccharides
  • Antioxidants
  • Tumor Suppressor Protein p53
  • Cyclin-Dependent Kinase Inhibitor p21