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Ibuprofen and glutathione conjugate as a potential therapeutic agent for treating Alzheimer's disease.
Arch Pharm (Weinheim) 2011; 344(3):139-48AP

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.

Authors+Show Affiliations

Dipartimento di Scienze del Farmaco, Università "G. D'Annunzio", Chieti, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21384412

Citation

Pinnen, Francesco, et al. "Ibuprofen and Glutathione Conjugate as a Potential Therapeutic Agent for Treating Alzheimer's Disease." Archiv Der Pharmazie, vol. 344, no. 3, 2011, pp. 139-48.
Pinnen F, Sozio P, Cacciatore I, et al. Ibuprofen and glutathione conjugate as a potential therapeutic agent for treating Alzheimer's disease. Arch Pharm (Weinheim). 2011;344(3):139-48.
Pinnen, F., Sozio, P., Cacciatore, I., Cornacchia, C., Mollica, A., Iannitelli, A., ... Di Stefano, A. (2011). Ibuprofen and glutathione conjugate as a potential therapeutic agent for treating Alzheimer's disease. Archiv Der Pharmazie, 344(3), pp. 139-48. doi:10.1002/ardp.201000209.
Pinnen F, et al. Ibuprofen and Glutathione Conjugate as a Potential Therapeutic Agent for Treating Alzheimer's Disease. Arch Pharm (Weinheim). 2011;344(3):139-48. PubMed PMID: 21384412.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ibuprofen and glutathione conjugate as a potential therapeutic agent for treating Alzheimer's disease. AU - Pinnen,Francesco, AU - Sozio,Piera, AU - Cacciatore,Ivana, AU - Cornacchia,Catia, AU - Mollica,Adriano, AU - Iannitelli,Antonio, AU - D'Aurizio,Eleonora, AU - Cataldi,Amelia, AU - Zara,Susi, AU - Nasuti,Cinzia, AU - Di Stefano,Antonio, Y1 - 2010/12/22/ PY - 2010/07/13/received PY - 2010/09/23/revised PY - 2010/09/24/accepted PY - 2011/3/9/entrez PY - 2011/3/9/pubmed PY - 2011/6/22/medline SP - 139 EP - 48 JF - Archiv der Pharmazie JO - Arch. Pharm. (Weinheim) VL - 344 IS - 3 N2 - 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. SN - 1521-4184 UR - https://www.unboundmedicine.com/medline/citation/21384412/Ibuprofen_and_glutathione_conjugate_as_a_potential_therapeutic_agent_for_treating_Alzheimer's_disease_ L2 - https://doi.org/10.1002/ardp.201000209 DB - PRIME DP - Unbound Medicine ER -