Salidroside attenuates beta amyloid-induced cognitive deficits via modulating oxidative stress and inflammatory mediators in rat hippocampus

Beta amyloid (A beta)-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 A beta-induced cognitive impairment in vivo. Rats received intrahippocampal A beta(1-40) 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 kappa B (NF-kappa B), inhibitor of kappa B-alpha (I kappa B alpha), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), receptor for advanced glycation end products (RAGE)). Our results confirmed that A beta(1-40) peptide caused learning and memory deficits in rats. Further analysis demonstrated that the NADPH oxidase-mediated oxidative stress was increased in A beta(1-40)-injected rats. Furthermore, NF-KB was demonstrated to be activated in A beta(1-40)-injected rats, and the COX-2, iNOS and RAGE expression were also induced by A beta(1-40). 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. (C) 2013 Elsevier B.V. All rights reserved.