title: 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: Guangxi Medical University, Nanning 530021, China.
authors: Ling
authors: L
authors: Wei
authors: Guangxi Medical University, Nanning 530021, China.
authors: Shujuan
authors: S
authors: Lv
authors: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
authors: Quanfang
authors: Q
authors: Huang
authors: Guangxi Medical University, Nanning 530021, China.
authors: Jinbin
authors: J
authors: Wei
authors: Guangxi Medical University, Nanning 530021, China.
authors: Shijun
authors: S
authors: Zhang
authors: Guangxi Medical University, Nanning 530021, China.
authors: Renbin
authors: R
authors: Huang
authors: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China; Ronald O. Perelman Department of Dermatology, NYU-Langone Medical Center, USA.
authors: Zhongpeng
authors: Z
authors: Lu
authors: Guangxi Medical University, Nanning 530021, China. Electronic address: gxLx60@163.com.
authors: Xing
authors: X
authors: Lin
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis; D018678:Cholinergic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced; D015394:Molecular Structure; D009473:Neuronal Plasticity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000009:adverse effects*; D017208:Rats, Wistar; D029921:Trifolium / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D018678:Cholinergic Agents; D007529:Isoflavones; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C543998:4'-methoxy-3',5,7-trihydroxyisoflavone; D000110:Acetylcholinesterase
keywords: Acetylcholine; Cognitive impairment; Pratensein; Synapse; β-amyloid