2-(2-benzofuranyl)-2-imidazoline and Alzheimer-Disease

Recent findings unveil the pharmacological modulation of imidazoline I

Topics: Alzheimer Disease; Animals; Apoptosis; Benzofurans; Cell Line, Tumor; Dose-Response Relationship, Drug; Humans; Imidazoles; Imidazoline Receptors; Ligands; Male; Mice; Molecular Structure; Oxidative Stress; Structure-Activity Relationship

Imidazoline I

Topics: Alzheimer Disease; Animals; Chlorocebus aethiops; Cycloaddition Reaction; Dogs; Female; HeLa Cells; Hippocampus; Humans; Imidazoles; Imidazoline Receptors; Ligands; Madin Darby Canine Kidney Cells; Mice; Molecular Structure; Nootropic Agents; Organophosphonates; Quantitative Structure-Activity Relationship; Vero Cells

Alzheimer's Disease (AD) is one of the commonest neural degeneration in aging population, and has become a global health challenge. 2-(2-benzofuranyl)-2-imidazoline (2-BFI) was reported to effectively improved the damage of patients with neuropathological disorders. In the present study, we investigated the effect of 2-BFI on the improvement of antioxidative, inflammation, and apoptosis in AD rats. Sprague-Dawley rats (2 months old, n=40) were used in this study and after injection of Aβ1-42 into hippocampal CA1 (Cornu Ammonis) region, the rats were given high, moderate and low dose of 2-BFI though intraperitoneal (i.p.) injection. Then spatial memory and navigation ability were analyzed by Morrize Water Maze. For the molecular testing, chemical colorimetry, ELISA and immunoblotting were performed to measure the activities of antioxidative enzymes, the abundance of immune cytokines and expression of apoptotic proteins, respectively. Hematoxylin and Eosin staining was used to analyze the pathological changes. We observed that 2-BFI significantly ameliorated the learning and memory abilities in rat models with AD by dosage treatment, as demonstrated by the shorten learning latency and greater times of travel across the platform quadrant. Additionally, reactive oxygen species (ROS) and malondialdehyde (MDA), were decreased after treatment of 2-BFI with dosage dependency, while the activities of superoxidase dismutase (SOD) and (GPX) Glutathione peroxidase were in turn enhanced, suggesting that 2-BFI could protect the antioxidative enzymes and reduce the oxidative stress in the hippocampus. Moreover, the expression of inflammatory factors including TNF-a and IL-1β were decreased after 2-BFI treatment. Additionally, the neuronal apoptosis was also attenuated, as shown by Western blot results. Taken together, the cognitive impairment in AD rats could be significantly improved by 2-BFI in a dose-dependent manner through suppressing oxidants accumulation, inhibiting of inflammatory response, as well as enhancing the neural viability.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Benzofurans; Disease Models, Animal; Dose-Response Relationship, Drug; Hippocampus; Imidazoles; Inflammation; Maze Learning; Neuroprotective Agents; Nootropic Agents; Oxidative Stress; Peptide Fragments; Random Allocation; Rats, Sprague-Dawley; Spatial Memory; Spatial Navigation