Neuro-Protective Effects Of Functional Foods On Alzheimer’S Disease
Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disease, which impairs memory and cognitive function. The prevalence of the pathology increases from 3% of the population at age 65 to 47% after the age of 85. Both environmental and genetic factors contribute to its pathogenesis. The neuropathological hallmarks of AD are characterized by the formation and deposition of extracellular amyloid plaques, and accumulation of intracellular hyperphosphorylated tau proteins known as neurofibrillary tangles. Formation of these Aβ plaques is thought to begin in the entorhinal complex and hippocampus, later progressing into the neocortex. The Ab peptide originates from processing of the amyloid precursor protein (APP). The observations regarding these plaques have led to the hypothesis that a reduction in amyloid plaque burden is expected to slow or halt the progression of AD.
Inflammation is another hallmark of AD, it occurs mainly around the amyloid plaques and is characterized by proinflammatory substances released from activated microglia and astroglia (Maczurek et al. , 2008). This microglial activation has been shown to increase the level of acetyl cholinesterase (AChE) activity and promote free radical generation that subjects the brain of an AD patient to increased oxidative stress. Reactive oxygen species (ROS) like hydrogen peroxide (H2O2) mediate the oxidative stress. ROS are known to attack cellular biomolecules and disrupt membrane integrity, thereby leading to apoptosis. Besides morphological alterations, AD is associated also with a markedly impaired cerebral glucose metabolism. AD progressively destroys a patient's memory, ability to learn, make judgments, communicate socially and carry out daily activities. In the course of the disease, short-term memory is affected first. Gradually, sufferers experience dramatic changes in personality and behaviour, such as anxiety, agitation, delusions or hallucinations.
Recently, natural foods and food-derived components, such as phenolic phytochemicals, have received a great deal of attention because they are safe and not considered to be medicine. Because of their antioxidative nature, their consumption may provide protection in neurological diseases such as AD. It was found that the consumption of fruit and vegetable juices containing high concentrations of polyphenols, at least three times per week, may play an important role in delaying the onset of AD. These polyphenols seem to be neuroprotective because of their ability to influence and modulate several cellular processes such as proliferation and apoptosis. Also because of their ability to cross the blood-brain barrier.
Subset of the flavonoids known as anthocyanins which are particularly abundant in brightly colored fruits have been shown to have potent antioxidant/anti-inflammatory activities and improve the adverse effects of the aging on nervous system or brain. Polyphenols resveratrol, catechins and quercetin are recent entries as antiaging agents. Maize bran polyphenol, ferulic acid is also reported to be beneficial in AD. A large prospective study indicated that intake of particularly the green leafy vegetables (e. g. , spinach and lettuce) and cruciferous vegetables (e. g. , broccoli and cauliflower) is related to reduced cognitive decline.
Turmeric
The principal bioactive component of turmeric is curcumin, it has been shown to reduce memory deficits in animal models of Alzheimer’s disease. Curcumin is relatively non-toxic and has few side effects. It is a strong antioxidant that seems to protect the brain from lipid peroxidation and nitric-oxide-based radicals. Recent studies have shown that curcumin is capable of crossing the blood-brain barrier in the central nervous system in sufficient quantities so as to reduce amyloid plaque burden. Rats treated with Ab, after incorporating with curcumin showed a reduction in oxidative stress, inflammation and cognitive deficits. It has been shown that curcumin can regulate extracellular amyloid deposition by regulating the signaling pathways behind the formation of plaques. In a study, rats were used to compare the effects of the NSAID, ibuprofen, and curcumin for their ability to protect against Aβ induced damage. Dietary curcumin, but not ibuprofen, suppressed oxidative damage and synaptophysin loss. Because of all these reasons including long history of safe use, curcumin is beneficial for AD prevention.
Grapes
Grape seed extract (GSE) is abundant in phenolic antioxidants and pro-anthocyanidins. Several studies have shown that the polyphenol enriched grape seed extract can reduce Aβ accumulation and protect against neurotoxicity and oxidative stress in vitro. One study reported a significant reduction in Aβ levels in brain and serum of transgenic mice fed with GSE by 33 and 44%, respectively than the control group fed a normal diet. Resveratrol is the nonflavonoid polyphenol abundant in grapes. Recently, it was reported that intraventricular injection of resveratrol lessens neurodegeneration in the hippocampus, and reduces learning impairment in mice model. Reports also suggested that resveratrol has the potential to reduce accumulation of amyloid protein in cell culture by enhancing proteolytic cleavage thereby alleviating inflammation and oxidative stress. Resveratrol has also been found to consistently prolong the life span.
Green tea
Green tea is a traditional drink that is obtained from the steamed and dried leaves of Camellia sinesis plant. Evidence indicates that polyphenols in green tea possess radical scavenging and iron chelating properties. The major flavonoid is epigallocatechin gallate (EGCG). In vitro and in vivo studies suggested EGCG is able to regulate proteolytic processing of APP, the precursor of Aβ. Moreover, long term supplementation of EGCG to mice showed a decrement in the level of APP. The antioxidant activity of green tea is supported in various studies. For instance, in rat brain tissue, green tea extract showed a significant reduction in lipid peroxidation. Green tea polyphenols, particularly catechin, are involved in metal chelation by inhibiting the formation of free radicals. The potential radical scavenging activity is due to the presence of trihydroxyl group on the B ring and gallate moiety at C-3 position which is unique to EGCG. The neuroprotective effect of EGCG on quinolinic acid induced cytotoxicity in human primary neuronal cells has also been demonstrated by a group of researchers. All above evidenced based benefits suggest that EGCG can be used as a neuroprotective agent for the treatment of AD.
Ginger
Ginger is a common spice that possesses culinary and medicinal properties. It is widely used as an extract, ginger tea or as a dietary adjunct. Gingerols, shagols, volatile oils such as bisabolene, zingiberene, and monoterpenes are the main bioactive compounds in ginger. The acetylcholinesterase (AChE) inhibitory activity of white and red ginger (extract) has been analysed in vitro, the results showed that effect of white ginger was comparatively higher. Inhibitory action of ginger on AChE and also on lipid peroxidation progressively leads to improved cognitive function in AD subjects. The putative mechanism behind the action is the ability of ginger extract to lessen free radical formation.
Blueberry
Blueberry is a rich source of cytoprotective antioxidant polyphenols called anthocyanins. Several studies have reported that blueberries have the potential to restore memory and cognitive deficits in brain. Preclinical studies suggest that blueberry supplementation is associated with enhanced memory and motor performance in aged animals. Studies conducted on 9 older adults with early memory decline showed marked improvement in memory and cognition following supplementation of wild blue berry juice for a period of 12 weeks. Improved paired associate learning and word list recall were also observed in the above study. Diets supplemented with 2% blueberry for a period of 8-10 weeks showed enhancement in hippocampal dysfunction in rats. Researchers have reported an inverse correlation between oxidative stress and blueberry administration in vitro. In one study, pre-treatment with blueberry extract was able to attenuate the emergence of oxidative stress related to AD.
Strawberry
The fruit strawberry contains various antioxidant polyphenols such as anthocyanins, gallic acid, tannins, vitamin C, vitamin E and carotenoids. Notably, strawberry extract has proven its potential to attenuate undesirable behavioral changes caused by irradiation. Supplementation of strawberry extract for a period of 8 weeks enhanced spatial learning and memory in rats induced with high dose of irradiation. Most importantly, strawberry diet showed improvement in hippocampal-dependent behaviors. Ellagitannins, the prominent antioxidant polyphenol in strawberry may be responsible for the beneficial effect. A study proposed and concluded that the protective effects of strawberry on neuronal cell viability are more than that of banana and orange. Therefore, additional consumption of strawberries may be beneficial for reducing the oxidative stress-induced risk of AD.
Walnuts
Walnut is enriched with beneficial fatty acids, α-tocopherol and polyphenols, especially ellagic acid. Epidemiological evidences suggest that a diet rich in walnut is associated with a lower incidence in neurodegenerative diseases. The potential inhibitory effect of walnut extract on Aβ fibril formation was assessed in a study. After 2–3 days of incubation, methanol extraction of walnut showed 90% of inhibition of Aβ fibril formation, also noticeable was its ability to defibrillize the pre-formed Aβ fibrils. Recently, researchers have shown that walnut extract can prevent Aβ-induced oxidative stress and cell death. The mechanism behind the favorable action is by lessening the generation of free radicals, and reducing membrane damage and DNA damage. Polyphenolic compounds in walnuts were concluded to be responsible for all these activities. Thus, a diet rich in walnuts may be a potential strategy for prevention and delaying the onset of AD.
