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July 5, 2011

Flavonoid prevents diabetic complications

Flavonoid prevents diabetic complications

On June 27, the journal PLoS ONE reported the discovery by Salk Institute for Biological Studies researchers of a benefit for fisetin in the prevention of several complications that can result from diabetes. Fisetin is a flavone found in abundance in strawberries, and in smaller quantities in other fruit and vegetables.

Salk Institute Cellular Neurobiology Laboratory head David Schubert, PhD and his associates had previously determined that fisetin increased the survival of cultured neurons, as well as improved memory in healthy mice. The current research evaluated the effects of fisetin in healthy control mice and Akita mice bred to develop type 1 diabetes. The latter develop kidney disease, retinopathy and neuropathies typical of human type 1 diabetics.

Although the diabetes in animals that received fisetin remained, kidney enlargement and urinary protein decreased compared to diabetic mice that did not receive the compound. Anxiety-related symptoms, which are a central nervous system complication that occurs in many human diabetics, were also reduced in animals that were given fisetin. "Most mice put in a large area become exploratory," lead author Pamela Maher, PhD observed. "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 researchers found a reduction in oxidative stress and C-reactive protein (a marker of inflammation), as well as decreased expression of the receptor for advanced glycation end products (RAGE) in the fisetin-treated mice. They also observed an increase in the activity of the enzyme glyoxalase 1, which promotes advanced glycation end product precursor removal. "We know that fisetin increases activity of the glyoxalase enzyme and may increase its expression," stated Dr Maher. "But what is important is that ours is the first report that any compound can enhance glyoxalase 1 activity."

"This manuscript describes for the first time a drug that prevents both kidney and brain complications in a type 1 diabetes mouse model," Dr Schubert announced. "Moreover, it demonstrates the probable molecular basis of how the therapeutic is working."

"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 added. "We will never know if a compound like fisetin works in humans until someone is willing to support a clinical trial."

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Health Concern Life Extension Highlight

Diabetes

The consequences of uncontrolled diabetes are severe: blindness, kidney failure, increased risk of heart disease, and painful peripheral nerve damage. Today, most practitioners focus treatment on strict blood sugar control. While diabetes is characterized by excess blood glucose (the form of sugar used by cells as energy), this simplified approach can actually hasten the progression of the most common form of diabetes and does nothing to address the damage it causes.

Glycation and oxidative stress are central to the damage caused by diabetes. Unfortunately, neither of them figures into conventional treatment for diabetes, which is generally concerned only with blood sugar control.

Glycation occurs when glucose reacts with protein, resulting in sugar-damaged proteins called advanced glycation end products (AGEs) (Kohn RR et al 1984; Monnier VM et al 1984). One well-known AGE among diabetics is glycated hemoglobin (HbA1c). HbA1c is created when glucose molecules bind to hemoglobin in the blood. Measuring HbA1c in the blood can help determine the overall exposure of hemoglobin to glucose, which yields a picture of long-term blood glucose levels.

Flavonoids are antioxidants that help reduce damage associated with diabetes. In animal studies, quercetin, a potent flavonoid, decreases levels of blood glucose and oxidants. Quercetin also normalizes levels of the antioxidants superoxide dismutase, vitamin C, and vitamin E. Quercetin is more effective at lower doses and ameliorates the diabetes-induced changes in oxidative stress (Mahesh T et al 2004).

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