Background: Possible mechanisms of Alzheimer Disease (AD) such as inflammation and oxidative stresses in the brain led us to investigate potential AD therapeutics of Melilotus officinalis, an herbal extract, with possible role as an anti-inflammatory and anti-oxidant agent. Among different genes which had important role in Sporadic AD (SAD), three genes including DAXX, NFkB and VEGF have shown significant statistical diversity in the brains of Alzheimer patients.
Methods: These genes were chosen to be investigated for neuroprotective effects of the extract by comparing the expression level in the hippocampus of Sporadic AD (SAD) rat model using quantitative polymerase chain reaction (qPCR) in the treated and untreated groups. In addition, therapeutic effects at the behavioral, learning and memory level by Morris Water Maze (MWM) test were investigated.
Results: The results represented significant decreased expression in Daxx, Nfkb and Vegf genes in the SAD rat's model treated with the herbal extract compared to the Streptozotocin-induced (STZ-induced) rats. Furthermore, no significant changes were seen in swimming distance and time for finding the hidden platform in the herbal-treated compared to the STZ-induced group. In memory level, no significant changes were observed among treated and untreated groups.
Conclusion: It seems that the herbal extract may have significant effect on Alzheimer-related gene expression changes but not on clinical levels.
Avicenna J Med Biotech 2017; 9(3): 133-137
Keywords: Alzheimer disease, Gene expression, Herbal medicine
Alzheimer Disease (AD) is the most common form of dementia with a predicted global incidence of 1 in every 85 cases by 2050 (1). It is characterized by progressive memory impairment and diminished cognitive performance which finally leads to death (2,3). The major pathological findings of AD brain are senile plaques, largely composed of extracellular amyloid-[beta] (A[beta]) peptides, and Neurofibrillary Tangles (NFTs), consisting of polymerized hyperphosphorylated tau protein. Sporadic or late-onset AD (>65 years) is the most common form of this disease, accounting for over 95% of cases (4,5).
Finding an effective method to prevent or slow down the disease process is a significant clinical challenge in treatment of Alzheimer's disease. Cholinesterase inhibitors have a limited clinical effect on the Alzheimer's symptoms (6). For years, drug developers focused on acetylcholinesterase inhibitors, with tacrine as the class leader (7). It showed relatively moderate activity in clinical trials; however, its therapeutic use was interrupted because of liver toxicity, which required close monitoring of patient's liver function (7). A new generation of acetylcholinesterase inhibitors, galantamine, donepezil, and rivastigmine with no liver toxicity were released in the market; however, therapeutic advantages were questionable (8). Animal models of AD play important role in the process of drug development. Their function mimics the disease in humans. Based on the hypothesis that is demonstrative of AD as type 3 diabetes which showed a consistent decrease in expression of insulin, insulin-like growth factors and their receptors in brains of AD patients, injection of STZ into the rat brain results in the same pattern (9). STZ causes phosphorylation of the tau protein, amyloid deposits, cognitive impairment, insulin desensitization and neuronal...