Zhang_2013_Behav.Brain.Res_244C_70

Beta amyloid (Abeta)-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 Abeta-induced cognitive impairment in vivo. Rats received intrahippocampal Abeta(1-40) injection were treated with salidroside (25, 50 and 75mg/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 kappaB (NF-kappaB), inhibitor of kappaB-alpha (IkappaBalpha), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), receptor for advanced glycation end products (RAGE)). Our results confirmed that Abeta(1-40) peptide caused learning and memory deficits in rats. Further analysis demonstrated that the NADPH oxidase-mediated oxidative stress was increased in Abeta(1-40)-injected rats. Furthermore, NF-kappaB was demonstrated to be activated in Abeta(1-40)-injected rats, and the COX-2, iNOS and RAGE expression were also induced by Abeta(1-40). However, salidroside (50 and 75mg/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.