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Neuroprotective Effect of Caffeic Acid Phenethyl Ester in A Mouse Model of Alzheimer's Disease Involves Nrf2/HO-1 Pathway

Fabiana Morroni, Giulia Sita, Agnese Graziosi, Eleonora Turrini, Carmela Fimognari, Andrea Tarozzi, Patrizia Hrelia

Aging Dis. 2018 Aug 1;9(4):605-622.

PMID: 30090650

Abstract:

Alzheimer's disease (AD) is a progressive pathology, where dementia symptoms gradually worsen over a number of years. The hallmarks of AD, such as amyloid β-peptide (Aβ) in senile plaque and neurofibrillary tangles, are strongly intertwined with oxidative stress, which is considered one of the common effectors of the cascade of degenerative events. The endogenous nuclear factor erythroid 2-related factor 2 (Nrf2) is the "master regulator" of the antioxidant response and it is known as an indicator and regulator of oxidative stress. The present study aimed to determine the potential neuroprotective activity of caffeic acid phenethyl ester (CAPE), a polyphenolic compound abundant in honeybee, against the neurotoxicity of Aβ1-42 oligomers (AβO) in mice. An intracerebroventricular (i.c.v.) injection of AβO into the mouse brain triggered increased reactive oxygen species levels, neurodegeneration, neuroinflammation, and memory impairment. In contrast, the intraperitoneal administration of CAPE (10 mg/kg) after i.c.v. AβO-injection counteracted oxidative stress accompanied by an induction of Nrf2 and heme oxygenase-1 via the modulation of glycogen synthase kinase 3β in the hippocampus of mice. Additionally, CAPE treatment decreased AβO-induced neuronal apoptosis and neuroinflammation, and improved learning and memory, protecting mice against the decline in spatial cognition. Our findings demonstrate that CAPE could potentially be considered as a promising neuroprotective agent against progressive neurodegenerative diseases such as AD.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP104594709 Caffeic acid phenethyl ester Caffeic acid phenethyl ester 104594-70-9 Price
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