Exploration of the mechanisms of improving learning and memory in the offspring of aging pregnant mice by supplementation with Paris polyphylla polysaccharide based on the P19-P53-P21 and Wnt/β-catenin signaling pathways

Abstract

Ethnopharmacological relevanceFirst recorded in “Sheng Nong's herbal classic”, Paris polyphylla is used to treat diseases, such as convulsions, head shaking and tongue fiddling, and epilepsy. Studies have shown that the ability of three Liliaceae polysaccharides in improving learning and memory may be related to the P19-P53-P21 and Wnt/β-catenin signaling pathways. Moreover, a link between these two signaling pathways and the possible neuroprotective impact of Paris polyphylla polysaccharide has been proposed. Aim of the studyWe explored the mechanisms of improving learning and memory in the offspring of pre-pregnant parental mice and D-galactose–induced aging pregnant mice by supplementation with P. polyphylla polysaccharide based on the P19-P53-P21 and Wnt/β-catenin signaling pathways. Study design and methodsAfter 3 weeks of supplementation of D-galactose–induced pre-pregnant parental mice with P. polyphylla polysaccharide component 1 (PPPm-1), the male and female parental mice mated in cages. The D-galactose–induced pregnant mice were continued to be supplemented with PPPm-1 for 18 days before delivery of the offspring. Behavioral experiments (Morris water maze and dark avoidance experiments) were conducted on the offspring mice born 48 days later to determine whether PPPm-1 had the effect of improving their learning and memory. Based on the P19/P53/P21 and Wnt/β-catenin signaling pathways, the mechanisms of PPPm-1 in improving learning and memory in offspring mice were further investigated. ResultsOffspring mice administered low- or high-dose PPPm-1 exhibited stronger motor and memory abilities in behavioral experiments than the aging model of offspring mice. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction revealed that the expressions of P19 and P21 mRNA and protein were inhibited in offspring mice administered low- and high-dose PPPm-1. However, P53 expression was inhibited in the low-dose PPPm-1 offspring group but promoted in the high-dose PPPm-1 offspring group. Additionally, PPPm-1 could effectively activate the Wnt/β-catenin signaling pathway, promote the expressions of Wnt/1, β-catenin, CyclinD1, and TCF-4 mRNA and protein, and inhibit GSK-3β mRNA and protein expression to improve the learning and memory abilities of offspring mice. ConclusionThus, PPPm-1 improved the learning and memory abilities in the offspring of aging pregnant mice by acting on the P19-P53-P21 and Wnt/β-catenin signaling pathways.