chrysin and Alzheimer-Disease

Alzheimer's disease (AD), the most common form of neurodegeneration disorder in adults, is becoming the overwhelming burden on the healthcare and economic system. In this study, chrysin derivative with the morpholine moiety was designed, synthesized and evaluated based on the multi targets directed ligands strategy for the treatment of AD centered with therapeutic attempts to restore metal homeostasis. It selectively coordinated with the important bio-metal ions related AD, especially Cu

Topics: Alzheimer Disease; Amyloid beta-Peptides; Copper; Flavonoids; Humans; Ligands; Metals; Molecular Structure

With the aging of the population intensifying, finding a cure or reasonable treatment for Alzheimer' disease (AD) has become an urgent priority. To target the multi-facets of AD, a class of chrysin derivatives (1-4) were rationally designed and synthesized by the multi-target-directed ligands (MTDLs) strategy, which were characterized by

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Butyrylcholinesterase; Cholinesterase Inhibitors; Crystallography, X-Ray; Drug Design; Flavonoids; Humans; Molecular Docking Simulation; Molecular Structure; Structure-Activity Relationship

Amyloid β plaques and neurofibrillary tangles are the characteristic features of Alzheimer's disease (AD). Plaques of amyloid β play a pivotal role in affecting cognitive functions and memory. Alzheimer's disease is a progressive neurodegenerative disease and is one of the leading causes of dementia worldwide. Several treatment strategies focusing on the amyloid cascade have been implemented to treat AD. The blood-brain barrier (BBB) poses the main obstructive barrier by refraining drugs from penetrating the brain. Nanotechnology is a promising research field for brain drug delivery using nanosized particles. Zebrafish is emerging as a model of interest to elaborate on brain targeting and nanotechnology-based therapeutics for neurodegenerative diseases. In the current study, we have synthesized and characterized chrysin-loaded chitosan nanoparticles (Chr-Chi NPs) and evaluated them for neuroprotection against amyloid-β-induced toxicity. We find that treatment with Chr-Chi NPs helps to retain memory, cognition, and synaptic connections, which are otherwise compromised due to Aβ

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Chitosan; Flavonoids; Nanoparticles; Neurodegenerative Diseases; Neuroprotection; Peptide Fragments; Plaque, Amyloid; Zebrafish

Islet amyloid polypeptide (amylin), consecrated by the pancreatic β-cells with insulin, has a significant role to play in maintaining homeostasis of islet cell hormones. Alzheimer's disease is the predominant source of dementia. However, its etiology remains uncertain; it appears that type 2 diabetes mellitus and other prediabetic states of insulin resistance contribute to the intermittent Alzheimer's disease presence. Amylin is abnormally elevated in Type II diabetes patients, accumulated into amylin aggregates, and ultimately causes apoptosis of the β-cells, and till date, its mechanism remains unclear. Several flavonoids have inhibitory effects on amylin amyloidosis, but its inhibition mechanisms are unknown. Screening a collection of traditional compounds revealed the flavone Chrysin, a potential lead compound. Chrysin inhibits amyloid aggregate formation according to Thioflavin T binding, turbidimetry assay. We report results of molecular interaction analysis of Chrysin with amylin which shows potent binding affinity against amylin. Pharmacokinetics and Drug likeness studies of Chrysin also suggest that it is a potential lead compound. Therefore, Chrysin prevented amylin aggregation.

Topics: Alzheimer Disease; Animals; Apoptosis; Cell Line, Tumor; Diabetes Mellitus, Type 2; Flavonoids; Humans; Insulin-Secreting Cells; Islet Amyloid Polypeptide; Molecular Docking Simulation; Protein Aggregation, Pathological; Protein Binding; Rats

Alzheimer's disease (AD) is the most common type of dementia, the exact etiology of the disease has not been known yet. The use of single-target drugs limits the efficacy of drugs and has certain side effects. In this study, the 'hidden' multi-target strategy was used in combination with chrysin's metal chelating site and rivastigmine's anti-cholinesterase pharmacophore to form an ester, which improves the hydrophobicity and protects the phenolic hydroxyl group at the same time. Four derivatives (1-4) were synthesized as the hidden multifunctional agents for AD therapy. Most of the compounds displayed good activities of anti-cholinesterase, antioxidant, appropriate blood brain barrier (BBB) penetration and certain inhibitory activity of β-amyloid (Aβ) aggregation. Compound 3 was demonstrated as the highest selective butyrylcholinesterase (BuChE) inhibitor and targeted both the catalytic active site (CAS) and the peripheral anion site (PAS). And it could be hydrolyzed by BuChE to release chrysin with good ability to chelate Cu

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Butyrylcholinesterase; Cholinesterase Inhibitors; Drug Design; Flavonoids; Humans; Molecular Docking Simulation; Structure-Activity Relationship

Alzheimer's disease (AD) is the most prevalent form of dementia. Amyloid-β25-35 (Aβ25-35), a well-established neurotoxicant, is reported to be involved in the etiology of AD. Chrysin (CN) with its wide range of biological activities in terms of reversing the neuronal damage once induced is limited due to its compromised bioavailability. Solid lipid nanoparticles (SLNs) on the other hand due to its improved protein stability, avoids proteolytic degradation, as well as sustained release of the incorporated molecules could be widely applied as a drug delivery vehicle. Hence, in the present investigation, we prepared CN loaded SLNs (CN-SLNs) and investigated its therapeutic role in alleviating Aβ25-35 administered neuronal damage. All the antioxidant enzymes and non-antioxidant enzyme in hippocampus were reduced significantly (P<0.01) in the Aβ25-35 injected group, whereas lipid peroxidation and acetylcholine esterase were increased significantly (P<0.01). These changes were restored significantly (P<0.01) by CN-SLNs (5mg/kg and 10mg/kg) and (P<0.05) by free CN (50mg/kg and 100mg/kg). Aβ25-35 also resulted in poor memory retention in behavioral tasks and histopathological sections of the hippocampal region showed the extent of neuronal loss which was thereby restored back on treatment with CN-SLNs and free CN. Our findings demonstrate that the therapeutic efficacy of CN could be attained at lower dose and also its oral bioavailability could be increased by encapsulating CN in SLNs. Thus the results suggest that CN-SLNs could be used as a potential therapeutic and a brain targeting strategy to combat the global burden of Alzheimer's disease.

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Ascorbic Acid; Drug Delivery Systems; Flavonoids; Glutathione; Hippocampus; Lipid Peroxidation; Male; Maze Learning; Motor Activity; Nanoparticles; Neurons; Neuroprotective Agents; Oxidative Stress; Peptide Fragments; Rats; Rats, Sprague-Dawley; Recognition, Psychology