Ibuprofen and Lipoic Acid Diamide as Co-Drug with Neuroprotective Activity: Pharmacological Properties and Effects in β-Amyloid (1–40) Infused Alzheimer's Disease Rat Model
Open accessAbstract
Both oxidative stress and inflammation are elevated in brains of Alzheimer's disease patients, but their pathogenic significance still remains unclear. Current evidence support the hypothesis that non-steroidal anti-inflammatory drugs (NSAIDs) and antioxidant therapy might protect against the development of Alzheimer's disease, and ibuprofen has the strongest epidemiological support. In the present work our attention was focused on (R)-α-lipoic acid considered as a potential neuroprotective agent in Alzheimer's disease therapy. In particular, we investigated a new co-drug (1) obtained by joining (R)-α-lipoic acid and ibuprofen via a diamide bond, for evaluating its potential to antagonize the deleterious structural and cognitive effects of β-amyloid (1–40) in an infused Alzheimer's disease rat model. Our results indicated that infusion of β-amyloid (1–40) impairs memory performance through a progressive cognitive deterioration; however, ibuprofen and co-drug 1 seemed to protect against behavioural detriment induced by simultaneous administration of β-amyloid (1–40) protein. The obtained data were supported by the histochemical findings of the present study: β-amyloid protein was less expressed in 1-treated than in ibuprofen and (R)-α-lipoic acid alone-treated cerebral cortex. Taken together, the present findings suggest that co-drug 1 treatment may protect against the cognitive dysfunction induced by intracerebroventricular infusion of β-amyloid (1–40) in rats. Thus, co-drug 1 could prove useful as a tool for controlling Alzheimer's disease-induced cerebral amyloid deposits and behavioural deterioration.
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In a rat model of AD following Aβ40 peptide injection, treatment with codrug 13 reduced Aβ40 peptide accumulation in cerebral cortex more significantly than treatment with ibuprofen or lipoic acid alone.
“After treatment with codrug 13, Aβ40 peptide accumulation was reduced in cerebral cortex in a more significant way than after treatment with 4 or 12 alone.90”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [90]
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- Authors
- Di Stefano, A., Sozio, P., Cerasa, L. S., Iannitelli, A., Cataldi, A., Zara, S., Giorgioni, G., & Nasuti, C.
- Affiliations
- University of Chieti-Pescara (IT)
- Università di Camerino (IT)
- Venue
- International Journal of Immunopathology and Pharmacology
- Publisher
- SAGE Publications
- Published
- 2010-04
- Volume
- 23
- Issue
- 2
- Pages
- 589-599
- ISSN
- 0394-6320 (ISSN-L)
- 2058-7384
- OpenAlex
- W123635004
- Cited by
- 26
- References
- 34
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 3
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- Locations
- International Journal of Immunopathology and Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Unicam Scientific Publications (University of Camerino) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- ibuprofen, alpha-lipoic acid, Alzheimer's disease, Aβ40, neuroprotection, memory impairment, cognitive impairment, oxidative stress, neuroinflammation, cerebral cortex, intracerebroventricular infusion, nonsteroidal anti-inflammatory drugs, antioxidants
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Ibuprofen, Immunohistochemistry, Thioctic Acid, Male, Motor Activity, Peptide Fragments, Tissue Distribution, Amyloid beta-Peptides, Rats, Wistar, Neuroprotective Agents, Maze Learning, Rats
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