Tags

Type your tag names separated by a space and hit enter

Caffeic acid phenethyl ester protects nigral dopaminergic neurons via dual mechanisms involving haem oxygenase-1 and brain-derived neurotrophic factor.
Br J Pharmacol. 2012 Jun; 166(3):1151-68.BJ

Abstract

BACKGROUND AND PURPOSE

Caffeic acid phenethyl ester (CAPE) is a component of honey bee propolis that can induce expression of haem 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, using a mouse model of dopaminergic neurodegeneration induced by intranigral injection of LPS and intrastriatal injection of 6-hydroxydopamine.

KEY RESULTS

CAPE protected dopaminergic neurons in slice cultures from IFN-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 MAPK inhibitor SB203580 prevented activation of NF-E2-related factor 2, attenuated increased expression of HO-1 and BDNF, and blocked the neuroprotective actions of CAPE. In the LPS-injected mouse model, daily intraperitoneal administration of CAPE protected dopaminergic neurons, up-regulated HO-1 and BDNF, and reduced the increase of activated microglia/macrophages. Neuroprotective effects 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 behaviour also in 6-hydroxydopamine hemiparkinsonian mice.

CONCLUSION AND IMPLICATIONS

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

Authors+Show Affiliations

Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamto, Japan.No 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

22224485

Citation

Kurauchi, Y, et al. "Caffeic Acid Phenethyl Ester Protects Nigral Dopaminergic Neurons Via Dual Mechanisms Involving Haem Oxygenase-1 and Brain-derived Neurotrophic Factor." British Journal of Pharmacology, vol. 166, no. 3, 2012, pp. 1151-68.
Kurauchi Y, Hisatsune A, Isohama Y, et al. Caffeic acid phenethyl ester protects nigral dopaminergic neurons via dual mechanisms involving haem oxygenase-1 and brain-derived neurotrophic factor. Br J Pharmacol. 2012;166(3):1151-68.
Kurauchi, Y., Hisatsune, A., Isohama, Y., Mishima, S., & Katsuki, H. (2012). Caffeic acid phenethyl ester protects nigral dopaminergic neurons via dual mechanisms involving haem oxygenase-1 and brain-derived neurotrophic factor. British Journal of Pharmacology, 166(3), 1151-68. https://doi.org/10.1111/j.1476-5381.2012.01833.x
Kurauchi Y, et al. Caffeic Acid Phenethyl Ester Protects Nigral Dopaminergic Neurons Via Dual Mechanisms Involving Haem Oxygenase-1 and Brain-derived Neurotrophic Factor. Br J Pharmacol. 2012;166(3):1151-68. PubMed PMID: 22224485.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Caffeic acid phenethyl ester protects nigral dopaminergic neurons via dual mechanisms involving haem oxygenase-1 and brain-derived neurotrophic factor. AU - Kurauchi,Y, AU - Hisatsune,A, AU - Isohama,Y, AU - Mishima,S, AU - Katsuki,H, PY - 2012/1/10/entrez PY - 2012/1/10/pubmed PY - 2012/10/12/medline SP - 1151 EP - 68 JF - British journal of pharmacology JO - Br J Pharmacol VL - 166 IS - 3 N2 - BACKGROUND AND PURPOSE: Caffeic acid phenethyl ester (CAPE) is a component of honey bee propolis that can induce expression of haem 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, using a mouse model of dopaminergic neurodegeneration induced by intranigral injection of LPS and intrastriatal injection of 6-hydroxydopamine. KEY RESULTS: CAPE protected dopaminergic neurons in slice cultures from IFN-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 MAPK inhibitor SB203580 prevented activation of NF-E2-related factor 2, attenuated increased expression of HO-1 and BDNF, and blocked the neuroprotective actions of CAPE. In the LPS-injected mouse model, daily intraperitoneal administration of CAPE protected dopaminergic neurons, up-regulated HO-1 and BDNF, and reduced the increase of activated microglia/macrophages. Neuroprotective effects 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 behaviour also in 6-hydroxydopamine hemiparkinsonian mice. CONCLUSION AND IMPLICATIONS: CAPE is a novel type of neuroprotective agent whose actions are mediated by both HO-1 and BDNF. These findings may provide novel clues to develop neuroprotective agents for treatment of neurodegenerative disorders. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/22224485/Caffeic_acid_phenethyl_ester_protects_nigral_dopaminergic_neurons_via_dual_mechanisms_involving_haem_oxygenase_1_and_brain_derived_neurotrophic_factor_ L2 - https://doi.org/10.1111/j.1476-5381.2012.01833.x DB - PRIME DP - Unbound Medicine ER -