Natural fruits, nuts, herbs and vegetables constitute a wide array of biologically active compounds including ferulic acid, anthocyanins, ellagic acid, punicagins, flavonols, phenolic acids and very important micronutrients such as phosphorus, iron, potassium and calcium, that are found abundantly in the plant kingdom.
Some of these natural products are effective in treating or preventing the majority of cardiovascular, metabolic and neurodegenerative diseases.
COUNTRIES: USA, Oman, Australia
CONDUCTED BY:National Institute of Health, Rockville, USA; College of Medicine and Health Sciences Muscat, Oman; Diseases Reseach Centre, Sydney, Australia.
PUBLISHED ON: Plos one
Alzheimer’s disease (AD) is a devastating age-related neurodegenerative disease with no specific treatment at present. The APPsw/Tg2576 mice exhibit age-related deterioration in memory and learning as well as amyloid-beta (Aβ) accumulation, and this mouse strain is considered an effective model for studying the mechanism of accelerated brain aging and senescence. The present study was aimed to investigate the beneficial effects of dietary supplements pomegranate, figs, or the dates on suppressing inflammatory cytokines in APPsw/Tg2576 mice. Changes in the plasma cytokines and Aβ, ATP, and inflammatory cytokines were investigated in the brain of transgenic mice. Significantly enhanced levels of inflammatory cytokines IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, TNF-α and Eotaxin activity were decreased by administration of the diet supplements containing pomegranates, figs, or dates. In addition, putative delays in the formation of senile plaques, as indicated by a decreasing tendency of brain Aβ1–40 and Aβ1–42 contents, were observed. Thus, novel results mediated by reducing inflammatory cytokines during aging may represent one mechanism by which these supplements exert their beneficial effects against neurodegenerative diseases such as AD.
Effect of pomegranates, figs, or date palm fruits on Aβ content in AD model mice.
In brain, the cerebrum or the cortex is the largest portion of the brain and performs most of the brain’s function. The cerebrum is divided into right and left hemispheres that are made of nerve cells which are connected by axons carrying the signals between the peripheral organs and the nerve cells. The hippocampus, an elaboration of the edge of the cerebral cortex and located in the cerebral hemisphere, is responsible for learning and memory, specifically converting temporary memories into permanent memories. These represent some regions of the brain that are susceptible to damage in neurodegenerative diseases. After measuring the levels of plasma cytokine levels, we next determined the levels of Aβ1–40 and Aβ1–42, since the accumulation of Aβ peptides activate neuro-inflammation in AD. Brain samples were collected from the untreated control or animals supplemented with pomegranates, figs or dates. The basal levels of Aβ1–40 in the cortex of control WT mice were 2105.35 ± 160.31 pg/mL and 1.36-fold higher than hippocampus (1540.26 ± 117.28 pg/mL) (Fig. 2A). Similarly, the basal levels of Aβ1–42 in the cortex of control wild-type was 1524.21 ± 95.50 pg/mL and 3.43-fold higher than hippocampus (452.08 ± 34.42 pg/mL) (Fig. 2A). The levels of Aβ1–40 in control TG (APPsw/Tg2576) were 4552.28 ± 348.45 pg/mL, which is significantly higher than that of control wild type (3906.95 ± 299.05 pg/mL) (Fig. 2A & B). The levels of Aβ1–40 in the brains of animals supplemented with the pomegranate diet decreased significantly (30.01% and 32.24%) in the cortex and hippocampus, respectively. The Aβ1–42 levels were 1956.33 ± 148.97 and 658.11 ± 50.11 pg/mL in the cortex and hippocampus, respectively. These levels in cortex and hippocampus were significantly decreased by 38.50% and 57.88% respectively (Fig. 2A & B). Supplementation of pomegranates significantly reduced the levels of Aβ1–40 and Aβ1–42 in APPsw/Tg2576 mice. This degrees of suppression of Aβ peptide levels were also observed in animals fed diets with figs or dates. The levels of Aβ1–40 in the cortex and the hippocampus in APPsw/Tg2576 mice were high and the levels of Aβ1–42 in the cortex, were ~25–40% less than that of Aβ1–40. Interestingly, the levels of Aβ1–42 in hippocampus were estimated to be ~60–70% less than the levels of Aβ1–40, suggesting that the Aβ1–40 peptide is the major aggregated peptide observed in AD.
Natural fruits, nuts, herbs and vegetables constitute a wide array of biologically active compounds including ferulic acid, anthocyanins, ellagic acid, punicagins, flavonols, phenolic acids and very important micronutrients such as phosphorus, iron, potassium and calcium, that are found abundantly in the plant kingdom. They are gaining interest due to their beneficial properties and with minimum side effects. Some of these natural products are effective in treating or preventing the majority of cardiovascular, metabolic and neurodegenerative diseases. Antioxidant activity is the key factor of all flavonoids by which they mediate the beneficial effects against the majority of many different diseases. The actions of dietary flavonoids involve a number of effects within the brain, such as modulation of neuronal signaling and the protection against neuronal losses. An extensive study on structure-function relationships of flavonoid activities provides valuable information for rationale drug designs of future pharmaceuticals in the prevention and treatment of several life-threatening diseases.
In conclusion, the pomegranates, figs, and date palm fruits grown in Oman provide possible protection against the inflammation in Tg2576 AD mouse brain and the mechanisms of protection may be related to their antioxidant activities of phenolic constituents (Fig. 4). Based on the in vivo experimental studies and the active ingredient profiles, it can be concluded that these fruits showed promising therapeutic potential against neurodegenerative diseases including AD, that areassociated with elevated inflammation. However, these results warrant further investigation of the mechanisms by which anti-inflammatory properties of these fruits can exert such beneficial effects on the brain in AD-like models.