Role of Polyphenols in Alleviating Alzheimer's Disease: A Review.

Alzheimer's Disease (AD) is a successive neurodegenerative disorder in the aged population. Many chemicals and phytochemicals are used to treat AD. Polyphenols which occur widely in various fruits, vegetables, beverages, and some other plant sources are gaining importance in AD treatment. Polyphenols comprise various subcategories, such as phenolic acids, lignans, tannins, stilbenes, hydroxybenzoic acid, hydroxycinnamic acid, and flavonoids. These compounds, as sole entities or in combination, can be used for treating AD because they have an abundance of antioxidants that are reported to be effective in free radical scavenging, metal ion chelating, and anti-inflammatory activities. Polyphenols of various plant origins have been studied, and these have been supported by in vitro assays and in vivo studies in rodents. These molecules protect neurons against oxidative stress and deposition of amyloid-ß (Aß) and tau proteins which play a vital role in the pathogenesis of AD. Consumption of wine and other foods rich in polyphenols has a beneficial effect on the neuronal signaling pathways, playing a vital role in shielding neuronal cells from neurodegeneration. Their ability to reduce free radicals and chelate metals are of great advantage. In this review, we highlight the various polyphenols that inhibit neuronal damage and progression of AD while also providing a cure. Some of the polyphenols covered are hesperidin, resveratrol, curcumin, catechin, kaempferol, and quercetin. The mechanisms of the actions of three polyphenols are also elaborated.

Fucoidan serves a neuroprotective effect in an Alzheimer's disease model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes memory and cognitive deficits. The present study was carried out to evaluate the protective effects of fucoidan in monocrotophos induced AD in Drosophila melanogaster. In silico studies showed that fucoidan exhibited binding energy of -9.3 kcal with proteins. Consistent with this, fucoidan, in a dose and time-dependent fashion, had inhibitory activity against cholinergic and monoamine-metabolized enzymes in vitro. Fucoidan inhibited the increase in total mRNA and protein in monocrotophos fed flies and prevented changes in biochemicals, neurochemicals and latency time of locomotor, learning and memory induced by monocrotophos. Together, the findings show that fucoidan serves a neuroprotective effect in Alzheimer's disease model in D. melanogaster.

Hesperidin ameliorates cognitive dysfunction, oxidative stress and apoptosis against aluminium chloride induced rat model of Alzheimer's disease.

BACKGROUND/AIMS: Deregulation of metal ion homeostasis has been assumed as one of the key factors in the progression of neurodegenerative diseases. Aluminium (Al) has been believed as a major risk factor for the cause and progression of Alzheimer's disease (AD). In our lab, we have previously reported that hesperidin, a citrus bioflavonoid reversed memory loss caused by aluminium intoxication through attenuating acetylcholine esterase activity and the expression of Amyloid ß biosynthesis related markers. Al has been reported to cause oxidative stress associated apoptotic neuronal loss in the brain. So in the present study, protective effect of hesperidin against aluminium chloride (AlCl3) induced cognitive impairment, oxidative stress and apoptosis was studied. METHODS: Male Wistar rats were divided into control, AlCl3 treated (100 mg/kg., b.w.), AlCl3 and hesperidin (100 mg/kg., b.w.) co-treated and hesperidin alone treated groups. In control and experimental rats, learning and memory impairment were measured by radial arm maze, elevated plus maze and passive avoidance tests. In addition, oxidative stress and expression of pro and anti-apoptotic markers were also evaluated. RESULTS: Intraperitoneal injection of AlCl3 (100 mg/kg., b.w.) for 60 days significantly enhanced the learning and memory deficits, levels of thiobarbituric acid reactive substances and the expression of Bax and diminished the levels of reduced glutathione, activities of enzymatic antioxidants and the expression of B-cell lymphoma-2 (Bcl-2) as compared to control group in the hippocampus, cortex, and cerebellum. Coadministration of hesperidin (100 mg/kg., b.w. oral) for 60 days prevented the cognitive deficits, biochemical anomalies and apoptosis induced by AlCl3 treatment. CONCLUSION: Results of the present study demonstrated that hesperidin could be a potential therapeutic agent in the treatment of oxidative stress and apoptosis associated neurodegenerative diseases including AD.

Tannoid principles of Emblica officinalis renovate cognitive deficits and attenuate amyloid pathologies against aluminum chloride induced rat model of Alzheimer's disease.

BACKGROUND/AIMS: Emblica officinalis is mentioned as a maharasayana in many Ayurvedic texts and promotes intelligence, memory, freedom from disease, longevity, and strength of the senses. The present study has been designed to explore the memory-enhancing effect of the tannoid principles of E. officinalis (EoT) at the biochemical, anatomical, behavioral, and molecular levels against aluminum chloride (AlCl3) induced Alzheimer's disease (AD) in rats. Aluminum is reported to have an important role in the etiology, pathogenesis, and development of AD. METHODS: Male Wistar rats were divided into control, AlCl3 treated, AlCl3 and EoT (50, 100, and 200 mg/kg bw) co-treated, and EoT (200 mg/kg bw) alone treated groups. In control and experimental rats, behavior tests including water maze and open field test, estimation of aluminum, assay of acetylcholinesterase (AChE) activity, and expression of amyloidogenic proteins were performed. RESULTS: Intraperitonial injection of AlCl3 (100 mg/kg bw) for 60 days significantly elevated the concentration of aluminum (Al), activity of AChE and protein expressions of amyloid precursor protein, A-beta1-42, beta-, and gamma-secretases as compared to control group in hippocampus and cortex. Co-administration of EoT orally to AlCl3 rats for 60 days significantly revert back the Al concentration, AChE activity, and A-beta synthesis-related molecules in the studied brain regions. The spatial learning, memory, and locomotor impairments observed in AlCl3 treated rats were significantly attenuated by EoT. CONCLUSION: Therefore, EoT may be a promising therapy in ameliorating neurotoxicity of aluminum, however further studies are warranted to elucidate the exact mechanism of action of EoT.