Neuroprotective Effect of Taxifolin Against Experimental Model of Alzheimer's Disease

Abstract

Background and Aim: Alzheimer’s disease (AD) is a progressive neurodegenerative disease that eventually leads to memory loss. It is a common type of “DEMENTIA”. AD is pathologically identified by accumulation of Amyloid-beta plaque and Neurofibrillary tangle (NFT) into neocortex, hippocampus, amygdala, diencephalon and basal ganglia. Neuroinflammation and oxidative stress, Alzheimer’s disease leads to brain damage. Taxifolin is a natural dihydroflavonol with good anti-inflammatory and anti-oxidative effects. This study focuses on the neuroprotective effect of taxifolin against the experimental models of Alzheimer’s disease. Experimental Method: Healthy SD rats were used in this study. We perform two different models. Rats were divided into 6 groups: Normal control group, Disease control (AlCl3) group, Treatment (taxifolin + AlCl3) group, Disease control (Scopolamine) group, Treatment (taxifolin + scopolamine), Standard treatment (donepezil + scopolamine) group. In AlCl3 induced Alzheimer’s disease model (AD), Normal control group was treated with normal Saline; Disease control group was treated with AlCl3 (25 mg/kg, i.p,) for 14 days. Treatment group treated AlCl3 for 7 days and then taxifolin (5 mg/kg i.p,) was co-administered with AlCl3 for another 7 days. Behaviour evaluation is performed on every alternative day. Lastly, animals were sacrificed and the brain was collected for biochemical and histopathological analysis. In scopolamine-induced Alzheimer’s disease model, disease control group was treated vehicle; treatment group was treated with taxifolin (5 mg/kg i.p,) for 7 days; Standard treatment group was treated with Donepezil (2 mg/kg i.p,) for 7 days. In all the 3 groups, scopolamine (2 mg/kg, i.p,) was administered on the 7th day after 30 minutes of vehicle/taxifolin administration. Behaviour assessment is performed before starting the treatment and after 2 hours of scopolamine treatment. Lastly, all of the animals were sacrificed and brains were isolated for histopathology and biochemical studies. Behaviour parameters are observed like (Pole climbing, Y-maze, and Morris water Maze test). Biochemical analyses are performed like myeloperoxidase, lipid peroxidation, superoxide dismutase, nitric oxide, catalase, and reduced glutathione. Biochemical analyses are performed like acetylcholinesterase, lipid peroxidation, superoxide dismutase, nitric oxide, catalase, and reduced glutathione, TLR4 expression. Results: Treatment (taxifolin + AlCl3) group was compared with disease control (AlCl3) group. Our results show that treatment with taxifolin in rats exposed to AlCl3 significantly mitigated the AlCl3-induced alterations in behavioural, biochemical, and histopathological. Treatment (taxifolin + scopolamine) group was compared with disease control (scopolamine) group. Our results show that treatment with taxifolin as well as donepezil in rats exposed to scopolamine significantly mitigated the scopolamine-induced behavioural, biochemical, and histopathological alterations. Conclusion: From the results, we can conclude that taxifolin is a promising therapeutic agent for the treatment and management of AD.