Pratensein attenuates Aβ-induced cognitive deficits in rats: enhancement of synaptic plasticity and cholinergic function.

Abstract

An isoflavone was isolated from Trifolium pratense using bioassay-guided screening. The structure of this natural compound was elucidated based on its spectral data, and it was identified as pratensein. The protective effect of pratensein was evaluated using a cognitive impairment model induced by injecting amyloid beta (1-42) (Aβ1-42) into the bilateral hippocampus of rats. The results showed that pratensein treatment significantly protected against Aβ1-42-induced cognitive impairments, as evidenced by the improvement in learning and memory and the attenuation of neuronal degeneration and apoptosis in hippocampus. Analysis of the potential mechanisms of action showed that pratensein significantly decreased inflammatory indicators such as MDA, NO, nNOS, IL-1β and TNF-α. Pratensein markedly decreased the content and deposition of β-amyloid peptide through regulating the expressions of Aβ-related genes including APP, BACE1, CatB, NEP and IDE. Moreover, pratensein significantly increased the expressions of synapse plasticity-related proteins, i.e., PSD-95, p-NMDAR1, p-CaMKII, p-PKACβ, PKCγ, p-CREB and BDNF. In addition, pratensein significantly decreased the activity of cholinesterase, then subsequently elevated the level of acetylcholine. In summary, our study indicated that pratensein may have a likely protective effect against Alzheimer's disease (AD) via improving synaptic plasticity and increasing cholinesterase activity.

• Authors: Ling Wei, Shujuan Lv, Quanfang Huang, Jinbin Wei, Shijun Zhang, Renbin Huang, Zhongpeng Lu, Xing Lin
• Journal: Fitoterapia (Fitoterapia) Vol. 101 Pg. 208-17 (Mar 2015) ISSN: 1873-6971 [Electronic] Netherlands
• PMID: 25665942 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Cholinergic Agents
• Isoflavones
• Neuroprotective Agents
• Peptide Fragments
• amyloid beta-protein (1-42)
• 4'-methoxy-3',5,7-trihydroxyisoflavone
• Acetylcholinesterase

Topics

• Acetylcholinesterase (metabolism)
• Alzheimer Disease
• Amyloid beta-Peptides (adverse effects)
• Animals
• Apoptosis
• Cholinergic Agents (pharmacology)
• Disease Models, Animal
• Hippocampus (drug effects)
• Isoflavones (pharmacology)
• Male
• Maze Learning (drug effects)
• Memory (drug effects)
• Memory Disorders (chemically induced)
• Molecular Structure
• Neuronal Plasticity (drug effects)
• Neuroprotective Agents (pharmacology)
• Peptide Fragments (adverse effects)
• Rats, Wistar
• Trifolium (chemistry)