Flavonoids represent two-fisted assault on diabetes, nervous system disorders: study
Fisetin, a naturally-occurring flavonoid found most abundantly in strawberries, lessens complications of diabetes. Courtesy of the Salk Institute for Biological Studies
A recent study from scientists at the Salk Institute for Biological Studies suggests that a strawberry a day (or more accurately, 37 of them) could keep not just one doctor away, but an entire fleet of them, including the neurologist, the endocrinologist, and maybe even the oncologist.
Investigations conducted in the Salk Institute's Cellular Neurobiology Laboratory (CNL) will appear in the June 27, 2011, issue of PLoS ONE. The report explains that fisetin, a naturally-occurring flavonoid found most abundantly in strawberries and to a lesser extent in other fruits and vegetables, lessens complications of diabetes. Previously, the lab showed that fisetin promoted survival of neurons grown in culture and enhanced memory in healthy mice. That fisetin can target multiple organs strongly suggests that a single drug could be used to mitigate numerous medical complications.
"This manuscript describes for the first time a drug that prevents both kidney and brain complications in a type 1 diabetes mouse model," says David Schubert, Ph.D., professor and head of the Cellular Neurobiology Laboratory and one of the manuscript's co-authors. "Moreover, it demonstrates the probable molecular basis of how the therapeutic is working."
Pam Maher, Ph.D., a senior staff scientist in the CNL, is the study's corresponding author. Maher initially identified fisetin as a neuroprotective flavonoid ten years ago. "In plants, flavonoids act as sunscreens and protect leaves and fruit from insects," she explains. "As foods they are implicated in the protective effect of the 'Mediterranean Diet.'"
Although her group's focus is neurobiology, Maher and colleagues reasoned that, like other flavonoids, fisetin might ameliorate a spectrum of disorders seen in diabetic patients. To test this, they evaluated effects of fisetin supplementation in Akita mice, a very robust model of type 1 diabetes, also called childhood onset diabetes.
Akita mice exhibit increased blood sugar typical of type 1 diabetes and display pathologies seen in serious human complications of both type 1 and 2 diabetes. Those include diabetic nephropathy or kidney disease, retinopathy, and neuropathies in which patients lose touch or heat sensations.
Mice fed a fisetin-enriched diet remained diabetic, but acute kidney enlargement-or hypertrophy-seen in untreated mice was reversed, and high urine protein levels, a sure sign of kidney disease, fell. Moreover, fisetin ingestion ameliorated anxiety-related behaviors seen in diabetic mice. "Most mice put in a large area become exploratory," says Maher. "But anxious mice tend not to move around. Akita mice showed enhanced anxiety behavior, but fisetin feeding restored their locomotion to more normal levels."
The study also defines a likely molecular mechanism underlying these effects. Researchers observed that blood and brain levels of sugars affixed to proteins known as advanced glycation end-products-or AGEs-were reduced in fisetin-treated compared to untreated Akita mice. These decreases were accompanied by increased activity of the enzyme glyoxalase 1, which promotes removal of toxic AGE precursors.
The discovery of an AGE-antagonizing enzyme upregulated by fisetin is very intriguing, because substantial evidence implicates high blood AGE levels with many if not most diabetic complications. "We know that fisetin increases activity of the glyoxalase enzyme and may increase its expression," says Maher. "But what is important is that ours is the first report that any compound can enhance glyoxalase 1 activity."
Interestingly, excessively high AGE levels also correlate with inflammatory activity thought to promote some cancers. In fact, studies published by others confirm that fisetin decreases tumorigenicity of prostate cancer cells both in culture and in animal models, which if supported would represent a major added incentive to eat your strawberries.
To ingest fisetin levels equivalent to those fed Akita mice, Maher estimates that humans would have to eat 37 strawberries a day, assuming that strawberry fisetin is as readily metabolizable by humans as fisetin-spiked lab chow is by mice. Rather than through diet, Maher envisions that fisetin-like drugs could be taken as a supplement.
Schubert notes that fisetin is also effective in mouse models of Alzheimer's disease. "We and others have shown that diabetes may be a risk factor for Alzheimer's disease, making identification of a safe prophylactic like fisetin highly significant," he says.
Maher acknowledges that the public may be suffering from flavonoid-fatigue, given media coverage of the promises of these compounds. "Polyphenolics like fisetin and those in blueberry extracts are found in fruits and vegetables and are related to each other chemically," she says. "There is increasing evidence that they all work in multiple diseases. Hopefully some combination of these compounds will eventually get to the clinic."
Schubert concurs that their findings only reinforce what common sense and our mothers told us was a healthy lifestyle. "Eat a balanced diet and as much freshly prepared organic food as possible, get some exercise, keep socially and mentally active and avoid sodas with sugar and highly processed foods since they can contain high levels of AGEs," he advises.
But he also worries that hoops that must be jumped through to bring a natural product like fisetin, as opposed to a totally synthetic drug, to clinical trials are daunting because it is difficult to protect patents on natural products. "We will never know if a compound like fisetin works in humans until someone is willing to support a clinical trial."
Provided by Salk Institute
- Natural Chemical Found in Strawberries Boosts Memory in Healthy Mice Oct 18, 2006 | not rated yet | 0
- Natural compound shows promise against Huntington's disease Nov 15, 2010 | not rated yet | 0
- Low carbohydrate diet may reverse kidney failure in people with diabetes Apr 20, 2011 | not rated yet | 0
- Study links diabetes and Alzheimer's disease Apr 30, 2008 | not rated yet | 0
- Chromium picolinate may lessen inflammation in diabetic nephropathy Sep 22, 2010 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
If you became brain-dead, would you want them to pull the plug?
15 hours ago I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
Genetic variations within and between populations
May 12, 2013 This paper (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1893020/) asserts these two different conclusions: ---Quote--- Thus the answer to the...
- More from Physics Forums - Medical Sciences
More news stories
In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...
Medical research 10 hours ago | 3.7 / 5 (3) | 0 |
Scientists investigating the interaction of a group of proteins in the brain responsible for protecting nerve cells from damage have identified a new target that could increase cell survival.
Medical research 15 hours ago | 5 / 5 (1) | 0
New findings by researchers carrying out experiments at the U.S. Department of Energy Office of Science's Advanced Photon Source (APS) help explain why some drugs that interact with two kinds of human serotonin ...
Medical research 17 hours ago | not rated yet | 0 |
Peptide molecules derived from the body's natural immune system can help boost the body's defence against life-threatening blood poisoning, joint University research has uncovered.
Medical research 18 hours ago | 4 / 5 (1) | 0 |
A new Montréal study conducted by Dr. May Faraj, associate research professor at the Université de Montréal and invited scientist at the IRCM, along with her research team and medical collaborators, shows ...
Medical research 18 hours ago | not rated yet | 0 |
Big names in medicine are set to give an upbeat assessment of the war on AIDS on Tuesday, 30 years after French researchers identified the virus that causes the disease.
34 minutes ago | not rated yet | 0
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
1 hour ago | not rated yet | 0 |
The neural machinery underlying our olfactory sense continues to be an enigma for neuroscience. A recent review in Neuron seeks to expand traditional ideas about how neurons in the olfactory bulb might encode information about ...
12 hours ago | not rated yet | 0 |
(Medical Xpress)—What if the quality of your work depends more on your focus on the piano keys or canvas or laptop than your musical or painting or computing skills? If target users can be convinced, they ...
13 hours ago | 3.7 / 5 (3) | 0 |
(AP)—A woman who lost both hands, her left leg and right foot after contracting a flesh-eating disease has been fitted with prosthetic hands.
1 hour ago | not rated yet | 0
(Medical Xpress)—Working with lab mice models of multiple sclerosis (MS), UC Davis scientists have detected a novel molecular target for the design of drugs that could be safer and more effective than current FDA-approved ...
10 hours ago | 5 / 5 (2) | 0 |