Ibuprofen and Glutathione Conjugate as a Potential Therapeutic Agent for Treating Alzheimer's Disease
Abstract
Non‐steroidal anti‐inflammatory drugs (NSAIDs) and antioxidant therapy might protect against the development of Alzheimer's disease (AD). In the present work, we synthesized a molecular combination of glutathione (GSH) and ibuprofen (IBU) via an amide bond and investigated its potential for targeted delivery of the parent drugs to neurons, where cellular oxidative stress and inflammation are related to AD. Evaluation of its physicochemical and in‐vitro antioxidant properties indicated that compound 1 exhibits good stability toward human plasma enzymatic activity, and, like GSH, displays in‐vitro free radical scavenging activity in a time and concentration‐dependent manner. The new compound was also assessed by infusion in a rat model for Alzheimer's disease for its potential to antagonize the deleterious structural and cognitive effects of β‐amyloid(1‐40). In behavioral tests of long‐term spatial memory, animals treated with codrug 1 performed significantly better than those treated with β‐amyloid (Aβ) peptide. Histochemical findings confirmed the behavioral data, revealing that Aβ protein was less expressed in cerebral cortex treated with 1 than that treated with IBU. Taken together, the present findings suggest that conjugate 1 treatment may protect against the oxidative stress generated by reactive oxygen species (ROS) and the cognitive dysfunction induced by intracerebroventricular (i.c.v.) infusion of Aβ(1‐40) in rats, and thus that codrug 1 could prove useful as a tool for controlling AD induced cerebral amyloid deposits and behavioral deterioration.
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Aβ protein was less expressed in the cerebral cortex of mice treated with 25 than in mice treated with 4.
“Moreover, histochemical studies revealed that Aβ protein was less expressed in cerebral cortex of mice treated with 25 than in mice treated with 4.”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [97]
In behavioral tests of long-term spatial memory, animals treated with ibuprofen-glutathione codrug (25) performed better than those treated with ibuprofen (4) and glutathione (23) singularly.
“The data obtained by behavioral tests of long-term spatial memory demonstrated that animals treated with 25 performed better than those treated with 4 and 23 singularly.”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [97]
The ibuprofen-glutathione codrug (25, referred to as 15 in the text) has an improved effect compared with ibuprofen (4) and glutathione (23).
“In this way, the authors could successfully conclude that 15 has an improved effect compared with 4 and 23.97”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [97]
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- Authors
- Pinnen, F., Sozio, P., Cacciatore, I., Cornacchia, C., Mollica, A., Iannitelli, A., D′Aurizio, E., Cataldi, A., Zara, S., Nasuti, C., & Di Stefano, A.
- Affiliations
- University of Chieti-Pescara (IT)
- Università di Camerino (IT)
- Venue
- Archiv der Pharmazie
- Publisher
- Wiley
- Published
- 2010-12-22
- Volume
- 344
- Issue
- 3
- Pages
- 139-148
- ISSN
- 0365-6233 (ISSN-L)
- 1521-4184
- OpenAlex
- W1984997269
- Cited by
- 49
- References
- 40
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 9
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archiv der Pharmazie (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Unicam Scientific Publications (University of Camerino) (submittedVersion)
- 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, glutathione conjugates, Alzheimer's disease, nonsteroidal anti-inflammatory drugs, antioxidant therapy, Aβ40, oxidative stress, reactive oxygen species, free radical scavenging, spatial memory, neuroprotection, cerebral cortex, plasma stability, codrugs
- MeSH terms
- Alzheimer Disease, Animals, Anti-Inflammatory Agents, Non-Steroidal, Antioxidants, Behavior, Animal, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Stability, Glutathione, Ibuprofen, Male, Peptide Fragments, Time Factors, Amyloid beta-Peptides, Drug Delivery Systems, Rats, Wistar, Reactive Oxygen Species, Oxidative Stress, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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