Therapeutic Potential of Plant Based HMG CoA Reductase Inhibitor-Berberine for Alzheimer’s Disease in ICV Induced Streptozotocin Rodent Model

Abstract

Background: Alzheimer's Disease (AD), is a progressive neurodegenerative disease, that results in memory loss, cognitive impairment and behavioral abnormalities. It is one of the most widely spread diseases and is common among elders. In AD there is an increase in the generation of ROS, RNS and phosphorylation of TAU. As a result, efforts to produce AD medications have centered on lowering the levels of Aβ (Amyoid β). Cholesterol stabilizes β-secretase and γ-secretase and promotes amyloidogenesis.Aim: The current work evaluated the therapeutic potential of plant-based berberine for Aβ clearance in a rodent model of AD via HMG CoA reductase inhibitory action.Materials and Methods: The olfactory sensibility (Buried pellet test), spatial memory (Morris water maze) and recognition memory (Novel Object Recognition Test-NORT) were used to evaluate berberines’ protective effects using female C57BL/6 mice. It was reported that Streptozotocin (STZ) causes memory loss and dysregulation of lipid metabolism.Results: The current investigation showed encouraging results in slowing the progression of AD by reducing Aβ deposition. The combination of Donepezil and berberine (DPZ-3.5 mg/kg and BBR-100 mg/kg/p.o) had significant improvement in behavioral parameters such as cognitive agility and olfactory function. BBR (100 mg/kg) has shown a significant decrease (40%) in total cholesterol levels compared to the disease group. Additionally, the group treated with BBR (100 mg/kg) alone showed a significant reduction in the Aβ amyloid deposition.Conclusion: This study shows that berberine slows the progression of AD by regulating the lipid metabolism as a result reducing the deposition of Aβ amyloid.

Keywords: Alzheimer’s disease; Aβ; Donepezil; Berberine; Streptozotocin