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Activated glutathione metabolism participates in protective effects of carnosic acid against oxidative stress in neuronal HT22 cells
- Source :
- Planta medica. 76(7)
- Publication Year :
- 2009
-
Abstract
- In our previous studies, we have reported that carnosic acid (CA) and carnosol (CS) originating from rosemary protects cortical neurons by inducing phase 2 enzymes, the induction of which was initiated by activation of the Keap1/Nrf2 pathway , , . In the present study we address the nature of the effector of these neuroprotective effects downstream of the phase 2 enzyme induction. From our results we conclude that activated glutathione (GSH) metabolism may participate in these protective effects. First, we performed cDNA microarray analysis in order to identify the gene(s) responsible for the actions and found that various enzymes involved in the metabolism of GSH (glutathione S-transferase, alpha 4; glutathione S-transferase, alpha 2; and formylglutathione hydrolase) constituted 3 of the top 5 CA-induced genes. The other 2 genes encoded phase 2 enzymes [NAD(P)H-quinone oxidoreductase1and aldehyde dehydrogenase family 3, subfamily A1]. Next, we compared the physiologically-active compounds originating from rosemary (CA, CS, luteolin, genkwanin, rosmarinic acid, caffeic acid, and verbenone) by 3 criteria (enhancement of total glutathione levels, transcriptional activation, neuroprotective effects). By all of these criteria, CA and CS were the most active. In contrast, the other compounds were only weakly active or totally inactive. These results suggest that pro-electrophilic compounds such as CA and CS may protect cortical neurons by causing the following sequential events: S-alkylation --> activation of the Keap1/Nrf2 pathway --> transcriptional activation --> induction of phase 2 enzymes --> activation of GSH metabolism --> neuroprotection.
- Subjects :
- Drug Evaluation, Preclinical
Pharmaceutical Science
Aldehyde dehydrogenase
medicine.disease_cause
Neuroprotection
Carnosol
Antioxidants
Analytical Chemistry
Cell Line
chemistry.chemical_compound
Mice
Drug Discovery
medicine
Animals
Oligonucleotide Array Sequence Analysis
Pharmacology
chemistry.chemical_classification
biology
Plant Extracts
Gene Expression Profiling
Organic Chemistry
Carnosic acid
Metabolism
Glutathione
Rosmarinus
Enzyme
Neuroprotective Agents
Complementary and alternative medicine
chemistry
Biochemistry
Abietanes
biology.protein
Molecular Medicine
Oxidative stress
Subjects
Details
- ISSN :
- 14390221
- Volume :
- 76
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Planta medica
- Accession number :
- edsair.doi.dedup.....97e10c9c3a02af6157b5d73c76c56126