Neuroprotective role of epigallocatechin-3-gallate, albeginin and melanoxetin in alzheimer's disease

Abstract

Background: Alzheimer's disease (AD) is a heterogeneous and progressive neurodegenerative disorder characterized by cognitive impairment and behavioral disturbances. Phytochemicals are considered safer alternatives and have shown significant efficacy in inhibiting cholinesterase, scavenging free radicals, inhibiting amyloid-β neurotoxicity, reducing inflammation, and interacting with neurotransmitters, thereby slowing down the progression of AD. Purpose: EGCG, is an antioxidant/anti-inflammatory that lowers amyloid-b and tau aggregation in AD models and improves cognition at preclinical dosages of 25–100 mg/kg/day and clinical doses of 200–800 mg/ Albeginin, a new flavonoid, reduces neuroinflammation in rats at 10–50 mg/kg/day, equal to 100–200 mg/day in humans. Melanoxetin, a phenolic molecule, chelates toxic metals, lowers ROS, and protects neurons at 15–40 mg/kg/day in animal models and 50–150 mg/day in humans. These chemicals show promise for Alzheimer's treatment. Study design: The study targeted specific AD-related proteins, including acetylcholinesterase (AChE), alpha serine/threonine-protein kinase (AKT-1), β-secretase-1 (BACE-1), cyclooxygenase-2 (COX-2), caspase-3, glycogen synthase kinase-3 (GSK-3), interleukin-6 (IL-6), mitogen-activated protein kinase-2 (MAPK-2), matrix metalloproteins-8 (MMP-8), N-methyl-d-aspartate receptor (NMDAR), Peptidyl arginine deiminase-2 (PAD-2), Presenilin-1 (PSEN-1), mitogen-activated protein kinase-14 (MAPK-14/P38), and tumor necrosis factor-alpha (TNF-α). Methods: Before conducting experimental work, molecular dynamic (MD) simulations were performed to assess the binding affinity of EGCG, albeginin, and melanoxetin against the selected targets. Sprague Dawley rats were injected with colchicine to induce AD, followed by treatment with the selected phytocompounds for three weeks. Results: In silico results indicated strong binding interactions of EGCG, albeginin, and melanoxetin with the target proteins. The rats treated with these phytocompounds showed a significant reduction in oxidative stress, inflammation, Aβ plaque formation, neurofibrillary tangles, and anticholinesterase activity. Conclusion: This is the first comprehensive study on the therapeutic role of EGCG, albeginin, and melanoxetin against AD. These phytocompounds demonstrate potential for better management of AD in the future.

Keywords

• Alzheimer
• Amyloid plaque
• Neurofibrillary tangles
• Neuroinflammation
• Phytocompounds