Abstract |
Beta amyloid (Aβ)-induced oxidative stress and chronic inflammation in the brain are considered to be responsible for the pathogenesis of Alzheimer's disease (AD). Salidroside, the major active ingredient of Rhodiola crenulata, has been previously shown to have antioxidant and neuroprotective properties in vitro. The present study aimed to investigate the protective effects of salidroside on Aβ-induced cognitive impairment in vivo. Rats received intrahippocampal Aβ1-40 injection were treated with salidroside (25, 50 and 75 mg/kg p.o.) once daily for 21 days. Learning and memory performance were assessed in the Morris water maze (days 17-21). After behavioral testing, the rats were sacrificed and hippocampi were removed for biochemical assays ( reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), acetylcholinesterase (AChE), acetylcholine (ACh)) and molecular biological analysis (Cu/Zn-SOD, Mn-SOD, GPx, nicotinamide adenine dinucleotide phosphate ( NADPH) oxidase, nuclear factor κB (NF-κB), inhibitor of κB-alpha (IκBα), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), receptor for advanced glycation end products (RAGE)). Our results confirmed that Aβ1-40 peptide caused learning and memory deficits in rats. Further analysis demonstrated that the NADPH oxidase-mediated oxidative stress was increased in Aβ1-40-injected rats. Furthermore, NF-κB was demonstrated to be activated in Aβ1-40-injected rats, and the COX-2, iNOS and RAGE expression were also induced by Aβ1-40. However, salidroside (50 and 75 mg/kg p.o.) reversed all the former alterations. Thus, the study indicates that salidroside may have a protective effect against AD via modulating oxidative stress and inflammatory mediators.
|
Authors | Jia Zhang, Yan-feng Zhen, Pu-Bu-Ci-Ren, Li-gang Song, Wei-na Kong, Tie-mei Shao, Xue Li, Xi-qing Chai |
Journal | Behavioural brain research
(Behav Brain Res)
Vol. 244
Pg. 70-81
(May 01 2013)
ISSN: 1872-7549 [Electronic] Netherlands |
PMID | 23396166
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2013 Elsevier B.V. All rights reserved. |
Chemical References |
- Amyloid beta-Peptides
- Glucosides
- Inflammation Mediators
- NF-kappa B
- Neuroprotective Agents
- Peptide Fragments
- Phenols
- Reactive Oxygen Species
- Receptor for Advanced Glycation End Products
- Receptors, Immunologic
- amyloid beta-protein (1-40)
- Nitric Oxide Synthase Type II
- Cyclooxygenase 2
- NADPH Oxidases
- Acetylcholinesterase
- rhodioloside
- Acetylcholine
|
Topics |
- Acetylcholine
(metabolism)
- Acetylcholinesterase
(metabolism)
- Amyloid beta-Peptides
(administration & dosage, antagonists & inhibitors, pharmacology)
- Animals
- Cognition Disorders
(chemically induced, metabolism)
- Cyclooxygenase 2
(metabolism)
- Glucosides
(administration & dosage, pharmacology)
- Hippocampus
(drug effects, metabolism)
- Inflammation Mediators
(metabolism)
- Male
- Maze Learning
(drug effects)
- Microinjections
- NADPH Oxidases
(metabolism)
- NF-kappa B
(metabolism)
- Neuroprotective Agents
(pharmacology)
- Nitric Oxide Synthase Type II
(metabolism)
- Oxidative Stress
(drug effects)
- Peptide Fragments
(administration & dosage, antagonists & inhibitors, pharmacology)
- Phenols
(administration & dosage, pharmacology)
- Rats
- Reactive Oxygen Species
(metabolism)
- Receptor for Advanced Glycation End Products
- Receptors, Immunologic
(metabolism)
|