title: Caffeic acid phenethyl ester protects against the dopaminergic neuronal loss induced by 6-hydroxydopamine in rats.
abstract: Caffeic acid phenethyl ester (CAPE) is a botanical compound abundant in honeybees' propolis. It has anti-inflammatory, antiviral, antioxidant, immunomodulatory and antitumor properties. Its beneficial effects against neurodegenerative diseases, including Parkinson's disease, have also been suggested and some mechanisms have been proposed. Mitochondrial damage and oxidative stress are critical events in neurodegeneration. Release of cytochrome c from mitochondria to cytosol and the downstream activation of caspase-3 have been suggested as targets of the protective mechanism of CAPE. Most of the studies addressing the protective effect of CAPE have been performed in cell culture. This is the first study to demonstrate the protective effect of CAPE against the dopaminergic neuronal loss induced by 6-hydroxydopamine (6-OHDA) in rats. It also demonstrates, for the first time, the inhibitory effect of CAPE on mitochondrial permeability transition (MPT), a mediator of neuronal death that triggers cytochrome c release and caspase-3 activation. Scavenging of reactive oxygen species (ROS) and metal chelation was demonstrated in the brain-affected areas of the rats treated with 6-OHDA and CAPE. Additionally, we demonstrated that CAPE does not affect brain mitochondrial function. Based on these findings and on its ability to cross the blood-brain barrier, CAPE is a promising compound to treat Parkinson's and other neurodegenerative diseases.
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto-USP, Avenida do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Barros Silva
authors.forename: N A G
authors.initials: NA
authors.lastname: Santos
authors.forename: N M
authors.initials: NM
authors.lastname: Martins
authors.forename: D A S
authors.initials: DA
authors.lastname: Ferreira
authors.forename: F
authors.initials: F
authors.lastname: Barbosa
authors.forename: V C
authors.initials: VC
authors.lastname: Oliveira Souza
authors.forename: A
authors.initials: A
authors.lastname: Kinoshita
authors.forename: O
authors.initials: O
authors.lastname: Baffa
authors.forename: E
authors.initials: E
authors.lastname: Del-Bel
authors.forename: A C
authors.initials: AC
authors.lastname: Santos
mesh_terms: D018663:Adrenergic Agents; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002109:Caffeic Acids / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects*; D000083162:Mitochondrial Permeability Transition Pore; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000517:prevention & control*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018663:Adrenergic Agents; D000975:Antioxidants; D002109:Caffeic Acids; D016166:Free Radical Scavengers; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018696:Neuroprotective Agents; D016627:Oxidopamine; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol