Pseudoginsenoside-F11 ameliorates okadiac acid-induced learning and memory impairment in rats via modulating protein phosphatase 2A.

Abstract

We have reported that pseudoginsenoside-F11 (PF11) can significantly improve the cognitive impairments in several Alzheimer's disease (AD) models, but the mechanism has not been fully elucidated. In the present study, the effects of PF11 on AD, in particular the underlying mechanisms related with protein phosphatase 2A (PP2A), were investigated in a rat model induced by okadaic acid (OA), a selective inhibitor of PP2A. The results showed that PF11 treatment dose-dependently improved the learning and memory impairments in OA-induced AD rats. PF11 could significantly inhibit OA-induced tau hyperphosphorylation, suppress the activation of glial cells, alleviate neuroinflammation, thus rescue the neuronal and synaptic damage. Further investigation revealed that PF11 could regulate the protein expression of methyl modifying enzymes (leucine carboxyl methyltransferase-1 and protein phosphatase methylesterase-1) in the brain, thus increase methyl-PP2A protein expression and indirectly increase the activity of PP2A. Molecular docking analysis, structural alignment and in vitro results showed that PF11 was similar in the shape and electrostatic field feature to a known activator of PP2A, and could directly bind and activate PP2A. In conclusion, the present data indicate that PF11 can ameliorate OA-induced learning and memory impairment in rats via modulating PP2A.

• Authors: Jinxiu Chu, Jian Wang, Lijuan Cui, Shuai Liu, Nina An, Jian Han, Xiaohang Che, Chunfu Wu, Jingyu Yang
• Journal: Mechanisms of ageing and development (Mech Ageing Dev) Vol. 197 Pg. 111496 (07 2021) ISSN: 1872-6216 [Electronic] Ireland
• PMID: 33957218 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Enzyme Activators
• Ginsenosides
• pseudoginsenoside F11
• Okadaic Acid
• Protein Phosphatase 2

Topics

• Animals
• Enzyme Activators (chemistry, pharmacology)
• Ginsenosides (chemistry, pharmacology)
• Learning Disabilities (chemically induced, drug therapy, enzymology)
• Male
• Memory Disorders (chemically induced, drug therapy, enzymology)
• Molecular Docking Simulation
• Okadaic Acid (toxicity)
• Protein Phosphatase 2 (chemistry, metabolism)
• Rats
• Rats, Sprague-Dawley