Caffeic acid phenethyl ester (CAPE) prevents inflammatory stress in organotypic hippocampal slice cultures.
Caffeic acid phenethyl ester (CAPE) is an antioxidant component of propolis, a natural product secreted by honeybee. Recent literature shows that CAPE inhibits nuclear factor kappa B (NFkappaB) activation in cell lines. Since NFkappaB was shown to be a crucial factor in neuroinflammation and to be associated with some neuropathologies, CAPE might reduce these disorders in brain too and have therapeutic applications. To test this hypothesis we used a model of endotoxic insult (interferon-gamma, followed by lipopolysaccharide) on rat organotypic hippocampal cultures. Cerebral inflammatory responses were strongly inhibited by CAPE (100 microM): reductions of NFkappaB nuclear activity, tumor necrosis factor alpha and nitric oxide productions were observed. At the dose of maximal effects (100 microM), an increase of cAMP-responsive element binding protein (CREB) activity, which anti-inflammatory role is well known, was seen. We compared CAPE effects with those of other drugs: anti-inflammatory as acetyl-salicylate and dexamethasone (glucocorticoid), antioxidant as pyrrolidine dithiocarbamate, or selective permeant inhibitor of NFkappaB as SN 50 peptide. These studies lead us to conclude that CAPE presents an interesting and original neuropharmacological profile compared to these drugs and might be helpful in the prevention of neurotoxic events due to excessive inflammatory reaction in brain. CAPE interferes with several effectors of neuroinflammation that might have complementary and synergic effects and allows a rather durable control since an acute treatment at the time of endotoxin exposure allows to control inflammatory factors for over 48 h.
Montpied
Pascale
P
Faculté de Pharmacie, CNRS-UMR 5094, 15 Avenue Charles Flahault, 34060 Montpellier Cedex 2, France. pascale.montpied@ibph.pharma.univ-montp1.fr
de Bock
Frédéric
F
Rondouin
Gérard
G
Niel
Gilles
G
Briant
Laurence
L
Courseau
Anne-Sophie
AS
Lerner-Natoli
Mireille
M
Bockaert
Joël
J
D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000627:therapeutic use*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D002109:Caffeic Acids / Q000627:therapeutic use*; D002467:Cell Nucleus / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D007371:Interferon-gamma / Q000009:adverse effects; D008070:Lipopolysaccharides / Q000009:adverse effects; D016328:NF-kappa B / Q000378:metabolism*; D009573:Nitrites / Q000032:analysis; D009924:Organ Culture Techniques; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000139:chemically induced / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D029742:Caenorhabditis elegans Proteins; D002109:Caffeic Acids; D017362:Cyclic AMP Response Element-Binding Protein; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; C400703:nos-2 protein, C elegans; D007371:Interferon-gamma; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol