DNC News

Purple Plants Protect the Brain: pomegranate, reseveratrol and blueberry

January 10, 2006

Subject: Recent research suggests certain plant extracts can either slow or reverse brain disease. Many of these extracts are purple.


The human brain considers the number three an important number is perception of cause and event. If something happens once it is seen as a random event. If it happens again, it's a coincidence. But if the same seeming cause and event is witnessed three times, the brain makes a generalization and considers the observation truth. Despite the best attempts of those well intentioned professors of statistics who taught me to think otherwise, my brain still follows this simple rule of three.


These thoughts are inspired by a number of recently published articles on plant extracts that protect the brain from damage, deterioration and possibly development of Alzheimer's disease. These plant extracts have something in common. They are all purple. They probably all contain high levels of polyphenol antioxidants like anthrocyanins, but we we're skipping the fancy chemistry today and making generalizations. They all are purple.


In June 2005 an article was published suggesting that pomegranate juice could protect newborn infants from brain damage caused by oxygen deprivation. [i] More recently Hartman and his colleagues at Loma Linda University published research suggesting pomegranate juice can prevent Alzheimer's disease.

Hartman worked with mice that were genetically predisposed to develop Alzheimer's, including buildups in the brain of a protein called beta-amyloid. The researchers separated the animals into two groups. Starting at 6 months of age, which is young adulthood in mice, one group had pomegranate-juice concentrate added to its drinking water in amounts that approximated a glass or two of the juice per day for a person. The second group received water without the concentrate but with as much sugar as the juice mix had.

As the mice aged, those drinking pomegranate juices did better in mazes and other tests of learning than did animals that drank the sugar water. When the researchers examined the animals' brains, the pomegranate-juice group had only about 50 percent as many beta-amyloid deposits, or plaques, as the sugar-water group had. [ii]

Several epidemiological studies have suggested that red wine consumption lowers risk of Alzheimer's. In 2003 a study linked this protective effect with resveratrol. Past newsletters on resveratrol have focused on how it stimulates apoptosis in cancer cells and may stimulate a ‘longevity factor.'

(Link: http://www.denvernaturopathic.com/resveratrol.html )

In November, 2005 another article was published on resveratrol and its effect on Alzheimer's. Resveratrol causes the break down of the beta-amyloid deposits or plaques that cause the disease. [iii] This is very exciting. Other antioxidants have been reported to prevent plaque formation but to reverse the disease process, if true, is a big deal.


Last on my list of purples are blueberries. A number of studies have been published over the last few years suggesting that blueberries were both protective and able to reverse some of the brain changes associated with cognitive decline. The newest study done in rats continues to confirm the earlier studies. [iv] Short term feeding with blueberries was shown to restore production of a specific brain protein which is used to respond to chemical stressors to that of a younger animal.


The color purple had great symbolism in ancient Rome . It was reserved for members of the ruling class. Members of the Roman Senate were permitted a ribbon of purple on their togas; only the emperor was allowed to wear a robe made entirely of purple. In the light of my new assumption that purple protects the brain, this symbolism takes on new meaning.


There are certainly other substances suggested for maintaining brain health that are not purple. Coenzyme Q-10, for example, is bright yellow. There are other exceptions to this generalization. There are probably other purple substances that have no benefit in protecting the brain. It's too late for me though, I've seen my three and my mind is made up.


Purple protects the brain. Period.






Pediatr Res. 2005 Jun;57(6):858-64. Epub 2005 Mar 17.

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Maternal dietary supplementation with pomegranate juice is neuroprotective in an animal model of neonatal hypoxic-ischemic brain injury.

Loren DJ , Seeram NP , Schulman RN , Holtzman DM .

Division of Neonatology, University of Washington , Seattle , WA 98195 , USA .

Neonatal hypoxic-ischemic brain injury remains a significant cause of morbidity and mortality and lacks effective therapies for prevention and treatment. Recently, interest in the biology of polyphenol compounds has led to the discovery that dietary supplementation with foods rich in polyphenols (e.g. blueberries, green tea extract) provides neuroprotection in adult animal models of ischemia and Alzheimer's disease. We sought to determine whether protection of the neonatal brain against a hypoxic-ischemic insult could be attained through supplementation of the maternal diet with pomegranate juice, notable for its high polyphenol content. Mouse dams were provided ad libitum access to drinking water with pomegranate juice, at one of three doses, as well as plain water, sugar water, and vitamin C water controls during the last third of pregnancy and throughout the duration of litter suckling. At postnatal day 7, pups underwent unilateral carotid ligation followed by exposure to 8% oxygen for 45 min. Brain injury was assessed histologically after 1 wk (percentage of tissue area loss) and biochemically after 24 h (caspase-3 activity). Dietary supplementation with pomegranate juice resulted in markedly decreased brain tissue loss (>60%) in all three brain regions assessed, with the highest pomegranate juice dose having greatest significance (p < or = 0.0001). Pomegranate juice also diminished caspase-3 activation by 84% in the hippocampus and 64% in the cortex. Ellagic acid, a polyphenolic component in pomegranate juice, was detected in plasma from treated but not control pups. These results demonstrate that maternal dietary supplementation with pomegranate juice is neuroprotective for the neonatal brain.

PMID: 15774834 [PubMed - indexed for MEDLINE]


[ii] Hartman, R.E., et al . 2005. Pomegranate juice decreases amyloid load and improves behavior in an APP transgenic mouse model with Alzheimer's disease-like pathology. Society for Neuroscience 35th Annual Meeting. Nov. 12-16. Washington , D.C.
R.E.Hartman1,3*; R.N.Schulman4; A.S.Shah1; M.Parsadanian1; D.M.Holtzman1,2
Alzheimers disease (AD) is the most common cause of dementia and affects more than 10% of individuals over the age of 65. There are currently no proven ways to delay the onset or slow the progression of AD. Epidemiological data suggest that diet can affect risk for AD. It has been found that food rich in polyphenols (e.g. blueberries, pomegranates, green tea) can be neuroprotective in animal models of hypoxic-ischemic brain injury and that some natural food products (e.g. curcumin) can decrease amyloid- (A) deposition. Pomegranate juice (PJ) has been shown to contain a very high concentration of polyphenols. We asked whether dietary supplementation of PJ influenced AD-like pathology and behavior in a mouse model of AD. Transgenic mice expressing a form of the amyloid precursor protein (APP) that causes a form of early-onset familial AD (Tg2576 or APPsw) received PJ or a sugar water control from 6 to 12.5 months of age. Mice treated with PJ had ~50% less A deposition in the hippocampus than control-treated mice. In addition, when tested behaviorally in the water maze, PJ-treated mice swam faster and exhibited better spatial learning performance than controls. Assessment of other biochemical markers of neuropathology is underway. These results, showing beneficial effects of PJ in an animal model of AD, suggest that further studies to validate and determine the mechanism of these effects as well as whether PJ can protect against AD in humans may be warranted.


J Biol Chem. 2005 Nov 11;280(45):37377-82. Epub 2005 Sep 14.

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Resveratrol promotes clearance of Alzheimer's disease amyloid-beta peptides.

Marambaud P , Zhao H , Davies P .

Litwin-Zucker Research Center for the Study of Alzheimer's Disease and Memory Disorders, North Shore-Long Island Jewish Institute for Medical Research, Manhasset, NY 11030, USA.

Several epidemiological studies indicate that moderate consumption of wine is associated with a lower incidence of Alzheimer's disease. Wine is enriched in antioxidant compounds with potential neuroprotective activities. However, the exact molecular mechanisms involved in the beneficial effects of wine intake on the neurodegenerative process in Alzheimer's disease brain remain to be clearly defined. Here we show that resveratrol (trans-3,4',5-trihydroxystilbene), a naturally occurring polyphenol mainly found in grapes and red wine, markedly lowers the levels of secreted and intracellular amyloid-beta (Abeta) peptides produced from different cell lines. Resveratrol does not inhibit Abeta production, because it has no effect on the Abeta-producing enzymes beta- and gamma-secretases, but promotes instead intracellular degradation of Abeta via a mechanism that involves the proteasome. Indeed, the resveratrol-induced decrease of Abeta could be prevented by several selective proteasome inhibitors and by siRNA-directed silencing of the proteasome subunit beta5. These findings demonstrate a proteasome-dependent anti-amyloidogenic activity of resveratrol and suggest that this natural compound has a therapeutic potential in Alzheimer's disease.

PMID: 16162502 [PubMed - in process]



Neurobiol Aging. 2005 Apr 30; [Epub ahead of print]

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Blueberry supplemented diet reverses age-related decline in hippocampal HSP70 neuroprotection.

Galli RL , Bielinski DF , Szprengiel A , Shukitt-Hale B , Joseph JA .

Neuroscience Laboratory, USDA-ARS Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA 02111, USA; Department of Psychology, Simmons College, 300 The Fenway, Boston, MA 02115-5898, USA.

Dietary supplementation with antioxidant rich foods can decrease the level of oxidative stress in brain regions and can ameliorate age-related deficits in neuronal and behavioral functions. We examined whether short-term supplementation with blueberries might enhance the brain's ability to generate a heat shock protein 70 (HSP70) mediated neuroprotective response to stress. Hippocampal (HC) regions from young and old rats fed either a control or a supplemented diet for 10 weeks were subjected to an in vitro inflammatory challenge (LPS) and then examined for levels of HSP70 at various times post LPS (30, 90 and 240min). While baseline levels of HSP70 did not differ among the various groups compared to young control diet rats, increases in HSP70 protein levels in response to an in vitro LPS challenge were significantly less in old as compared to young control diet rats at the 30, 90 and 240min time points. However, it appeared that the blueberry diet completely restored the HSP70 response to LPS in the old rats at the 90 and 240min times. This suggests that a short-term blueberry (BB) intervention may result in improved HSP70-mediated protection against a number of neurodegenerative processes in the brain. Results are discussed in terms of the multiplicity of the effects of the BB supplementation which appear to range from antioxidant/anti-inflammatory activity to signaling.

PMID: 15869824 [PubMed - as supplied by publisher]



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