amyloid-beta-peptides and rhodioloside

Alzheimer's disease (AD) is the most common type of senile dementia, which often develops in elderly or presenile individuals. As one of the pathological features of AD, amyloid β‑protein (Aβ) causes energy dysmetabolism, thereby inducing cellular damage and apoptosis. Salidroside is the main active component of the traditional Chinese medicine Rhodiola. Previous studies have demonstrated that salidroside exerts a regulatory role in energy metabolism. However, the role and the mechanism of action of salidroside in AD remain unclear. Therefore, the present study used Aβ1‑40 to induce damage in PC12 cells, thereby establishing a cell model of AD. In addition, salidroside treatment was performed to investigate the protective effect of salidroside and the underlying mechanisms. Aβ1‑40‑induced neuronal toxicity reduced cell viability and caused cellular damage. As a result, the expression level of nicotinamide phosphoribosyltransferase (NAMPT) decreased, the synthesis of nicotinamide adenine dinucleotide (NAD+; an energy metabolism‑associated coenzyme) became insufficient, and the NAD+/nicotinamide adenine dinucleotide hydride ratio was reduced. Administration of salidroside alleviated Aβ‑induced cell damage and increased the expression level of the key protein NAMPT and the synthesis of NAD+. The results of the present study demonstrate that salidroside exerts a protective effect on Aβ1‑40‑damaged PC12 cells. The underlying mechanism may be associated with the regulation of energy metabolism that relies predominantly on the NAMPT signaling pathway.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Cell Survival; Glucosides; Neuroprotective Agents; Nicotinamide Phosphoribosyltransferase; PC12 Cells; Peptide Fragments; Phenols; Rats; Rhodiola; Signal Transduction

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.

Topics: Acetylcholine; Acetylcholinesterase; Amyloid beta-Peptides; Animals; Cognition Disorders; Cyclooxygenase 2; Glucosides; Hippocampus; Inflammation Mediators; Male; Maze Learning; Microinjections; NADPH Oxidases; Neuroprotective Agents; NF-kappa B; Nitric Oxide Synthase Type II; Oxidative Stress; Peptide Fragments; Phenols; Rats; Reactive Oxygen Species; Receptor for Advanced Glycation End Products; Receptors, Immunologic