Wednesday, January 11, 2012

Propolis Component May Help Treat Neurodegenerative Disorders

Caffeic Acid Phenethyl Ester Protects Nigral Dopaminergic Neurons Via Dual Mechanisms Involving Heme Oxygenase-1 and Brain-Derived Neurotrophic Factor
British Journal of Pharmacology, Accepted manuscript online: 6 JAN 2012

Background and purpose: Caffeic acid phenethyl ester (CAPE) is a component of propolis from honeybee that can induce expression of heme oxygenase-1 (HO-1). Because HO-1 induction has been suggested to protect dopaminergic neurons in the substantia nigra, we examined the effect of CAPE in experimental models of dopaminergic neurodegeneration.

Experimental approach: Neuroprotective effect of CAPE was investigated in rat organotypic midbrain slice cultures and in vivo experimental mouse model of dopaminergic neurodegeneration by intranigral injection of lipopolysaccharide (LPS) and intrastriatal injection of 6-hydroxydopamine.

Key results: CAPE protected dopaminergic neurons in slice cultures from interferon-γ/ LPS-induced injury. The effect of CAPE was inhibited by zinc protoporphyrin IX, an HO-1 inhibitor, and by neutralizing antibody against brain-derived neurotrophic factor (BDNF). A p38 mitogen-activated protein kinase inhibitor SB203580 prevented activation of NF-E2-related factor 2, attenuated increased expression of HO-1 and BDNF, and blocked neuroprotective action of CAPE. In LPS-injected mouse model, daily intraperitoneal administration of CAPE protected dopaminergic neurons, upregulated HO-1 and BDNF, and reduced the increase of activated microglia/macrophages. Neuroprotective effect of CAPE against LPS-induced injury was prevented by zinc protoporphyrin IX or anti-BDNF antibody. CAPE protected dopaminergic neurons and alleviated methamphetamine-induced rotational behavior also in 6-hydroxydopamine hemi-parkinsonian mice.

Conclusions and implications: CAPE is a novel type of neuroprotective agent whose actions are mediated by both HO-1 and BDNF. These findings may provide a novel clue to develop neuroprotective pharmaceuticals for treatment of neurodegenerative disorders.

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