ethyl-ferulate and Neurodegenerative-Diseases

In recent years there has been a growing interest, supported by a large number of experimental and epidemiological studies, in the beneficial effects of some commonly used food-derived products in preventingvarious age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Spices and herbs often contain active phenolic substances endowed with potent antioxidative and chemopreventive properties. Curcumin is a phytochemical compound extracted from the rhizome of Curcuma Longa. It is the pigment responsible for the characteristic yellow color of Indian curry. Data from our and other laboratories demonstrated that curcumin, as well as some other polyphenols, strongly induce heme oxygenase 1 and Phase II detoxification enzymes in neurons and, by this activation, protect neurons against different modes of oxidative challenge. The potential role of curcumin as a preventive agent against brain aging and neurodegenerative disorders has been recently reinforced by epidemiological studies showing that in India, where this spice is widely used in the daily diet, there is a lower incidence of Alzheimer's disease than in the USA. These studies identify a novel class of compounds that could be used for therapeutic purposes as preventive agents against the acute neurodegenerative conditions that affect many in the world's increasingly ageing population.

Topics: Aging; Antioxidants; Brain; Caffeic Acids; Catechin; Curcumin; Diet; Flavonoids; Neurodegenerative Diseases; Neuroprotective Agents; Phenols; Phenylethyl Alcohol; Polyphenols

Ferulic acid ethyl ester (FAEE) is an ester derivative of ferulic acid, the latter known for its anti-inflammatory and antioxidant properties. Previous studies from our laboratory have shown that ferulic acid protects synaptosomal membrane system and neuronal cell culture systems against hydroxyl and peroxyl radical oxidation. FAEE is lipophilic and is able to penetrate lipid bilayer. Previous studies reported that FAEE reduces Alzheimer's amyloid beta peptide Abeta(1-42)-induced oxidative stress and cytotoxicity in neuronal cell culture by direct radical scavenging and by inducing certain antioxidant proteins. In the present study we tested the hypothesis that FAEE would provide neuroprotection against free radical oxidative stress in vivo. Synaptosomes were isolated from the gerbils that were previously injected intraperitoneally (i.p.) with FAEE or DMSO and were treated with oxidants, Fe(2+)/H(2)O(2) or 2,2-azobis(2-amidino-propane)dihydrochloride (AAPH). Synaptosomes isolated from the gerbil previously injected i.p. with FAEE and treated with Fe(2+)/H(2)O(2) and AAPH showed significant reduction in reactive oxygen species (ROS), levels of protein carbonyl, protein bound 4-hydroxynonenal (HNE, a lipid peroxidation product), and 3-nitrotyrosine (3-NT, another marker of protein oxidation formed by reaction of tyrosine residues with peroxynitrite) compared to Fe(2+)/H(2)O(2) or AAPH induced oxidative stress in synapotosomes isolated from the brain of gerbils that were previously injected with DMSO. The synaptosomes isolated from gerbil pre-injected with FAEE and subsequently treated with AAPH or Fe(2+)/H(2)O(2) showed induction of heme oxygenase (HO-1) and heat shock protein 70 (HSP-70) but reduced inducible nitric oxide synthase (iNOS) levels. These results are discussed with reference to potential use of this lipophilic antioxidant phenolic compound in the treatment of oxidative stress-related neurodegenerative disorders.

Topics: Aldehydes; Amidines; Animals; Caffeic Acids; Ferrous Compounds; Gerbillinae; Heme Oxygenase (Decyclizing); HSP70 Heat-Shock Proteins; Hydrogen Peroxide; Male; Neurodegenerative Diseases; Neuroprotective Agents; Nitrates; Nitric Oxide Synthase Type II; Oxidative Stress; Reactive Oxygen Species; Synaptosomes