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3-Acetyl coumarin alleviate neuroinflammatory responses and oxidative stress in aluminum chloride-induced Alzheimer's disease rat model.
- Source :
-
Inflammopharmacology [Inflammopharmacology] 2024 Apr; Vol. 32 (2), pp. 1371-1386. Date of Electronic Publication: 2024 Mar 06. - Publication Year :
- 2024
-
Abstract
- Alzheimer's disease (AD) is a neurodegenerative disorder that impairs mental ability and interrupts cognitive function. Heavy metal exposure like aluminum chloride is associated with neurotoxicity linked to neuro-inflammation, oxidative stress, accumulation of amyloid plaques, phosphorylation of tau proteins associated with AD like symptoms. The objective of the present investigation was to assess the effect 3-acetyl coumarin (3AC) in a rat model of AD. Preliminary screening was performed with SWISS ADME to check for the bioavailability of 3-AC and likeness score which proved favorable. 3-AC docked against Caspase 3, NF-κβ and tau protein kinase I exhibited good binding energies. Male rats were divided into six groups (n = 5). AlCl <subscript>3</subscript> (100 mg/kg BW) was administered for 28 days before starting treatment to induce AD. Normal control rats received vehicle. Treatment groups received 10, 20 and 30 mg/kg 3-AC for 28 days. Rivastigmine (2 mg/kg) was the standard. Behavioral tests (EPM, MWM) were performed at 7-day intervals throughout study period. Rats showed improved spatial memory and learning in treatment groups during behavioral tests. Rats were euthanized on day 28. Inflammatory markers (IL-1β, IL-16 and TNFα) exhibited significant improvement (p < 0.001) in treated rats. Oxidative stress enzymes (SOD, CAT, GSH, MDA) were restored. Caspase3 and NF-κβ quantified through qRT-PCR also decreased significantly (p < 0.001) when compared to disease control group. Levels of acetyl cholinesterase, dopamine and noradrenaline were also restored in treated rats significantly (p < 0.001). 3-AC treatment restored neuroprotection probably because of anti-inflammatory, anti-oxidant and anti-cholinesterase potential; hence, this can be considered a promising therapeutic potential alternative.<br /> (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
- Subjects :
- Rats
Male
Animals
Aluminum Chloride adverse effects
Aluminum Compounds therapeutic use
Aluminum Compounds toxicity
Chlorides toxicity
Chlorides therapeutic use
Rats, Wistar
Oxidative Stress
Antioxidants pharmacology
Inflammation drug therapy
Inflammation complications
Coumarins pharmacology
Coumarins therapeutic use
Disease Models, Animal
Alzheimer Disease chemically induced
Alzheimer Disease drug therapy
Neuroprotective Agents
Subjects
Details
- Language :
- English
- ISSN :
- 1568-5608
- Volume :
- 32
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Inflammopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38448794
- Full Text :
- https://doi.org/10.1007/s10787-024-01434-x