A “seeded-apple” a day. Some cultures believe that the fruit Adam and Eve picked from the tree of knowledge was the pomegranate (from the French pomme gamete, meaning seeded apple). If so, research suggests the fruit was a wise choice, at least in terms of cardiovascular health, A recent study by Claudio Napoli, a MED adjunct professor of medicine at the Whitaker Cardiovascular Institute and the Evans department of medicine, and Lou Ignarro, a UCLA pharmacology professor and a 1998 Nobel laureate in medicine, in collaboration with colleagues at the Mayo Clinic and the University of Novara, Italy, shows that pomegranate juice has both preventive and therapeutic effects for coronary arteries.

Previous studies have suggested that the antioxidants in pomegranate juice may reduce atherosclerosis, the build-up of fatty deposits in arteries, as well as contribute to a reduction in oxidative stress — a metabolic imbalance in cells that can result in an accumulation of free radicals and cell damage. Napoli’s study focused on how pomegranate juice affects endothelial cells that line blood vessels and produce nitric oxide, a potent vasodilator that protects vessels by allowing them to relax. The study specifically looked at epithelial cells subjected to high levels of disturbed shear stress, caused by blood rushing over an uneven surface. This type of stress can interfere with the normal functioning of epithelial cells, much like rapids have a stronger effect on a riverbed than does a smooth flowing stream.

Napoli and his colleagues tested the effects of pomegranate juice in vitro, using cultured endothelial cells from the human coronary artery that were exposed to high levels of shear stress. They also looked at the juice’s effects in vivo on mice specially bred with high levels of cholesterol and at various stages of atherosclerosis.

They found that treatment with pomegranate juice increased nitric oxide production in cells undergoing high levels of shear stress. They also found that the progression

of atherosclerosis was significantly reduced in mice that drank pomegranate juice.

Pomegranate juice is high in polyphenols, a group of antioxidant-rich natural chemicals found in many fruits and vegetables. According to the researchers, the polyphenol level in pomegranate juice is higher than in other natural juices, such as blueberry, cranberry, and orange, as well as in red wine.

The research was published in the March 21 Proceedings of the National Academy of Sciences.

Repeating problems. People with Huntington’s disease (HD), a degenerative brain disorder with no effective treatment or cure, gradually lose their ability to walk, talk, think, and reason, and eventually die of the disease. It is estimated that about one in every 10,000 persons worldwide has this devastating disease.

Huntington’s disease is caused by a single abnormal gene that has many more repeats of the DNA bases cytosine, adenine, and guanine (CAG) than are in the normal gene. People who do not have HD have fewer than 35 CAG repeats in a row, while those with the disease may have up to hundreds of such repeats. The abnormal gene in turn produces a protein with multiple repeats of glutamine, which tend to aggregate, forming insoluble clumps within neurons, and possibly killing them off. Huntington’s is one of a number of related diseases known as polyQ, or polyglutamine (many glutamines), expansion disorders, in which a gene has these repeats.

Xiaoquian Zhang and Anatoli Meriin, MED biochemistry research associates, and Michael Sherman, a MED associate professor of biochemistry, recently published a study in which they identified a small molecule that inhibits the formation of polyQ aggregates and suppresses neurodegeneration in a living organism. They collaborated with colleagues at Massachusetts General Hospital, Kings College, London, the Max Delbruck Center for Molecular Medicine, Berlin, the University of California, Irvine, and the Massachusetts Institute of Technology.

They began by screening some 16,000 small molecules in yeast that had been genetically modified to carry a gene comparable to the mutant HD gene. They found nine small molecules that inhibited polyQ aggregation in these yeast cells, four of which were also found to reduce polyQ aggregation in mammalian cells with the genetic defect. The researchers produced variations on the four molecules and tested them in the cultured brain cells of mice with HD to identify the most potent molecule. The most effective of these was tested in living fruit flies having the defective HD gene and was found to help prevent neurodegeneration.

Better understanding of how to inhibit polyQ protein aggregates and neuronal degeneration in HD may also shed light on other diseases. Both Alzheimer’s and Parkinson’s, as well as another group of neurodegenerative diseases called prion diseases, have characteristic amyloid-like protein aggregate deposits, similar to those found in HD, that accumulate in and destroy neurons. Finding small molecules that inhibit the aggregation of disease proteins may facilitate the development of new treatment strategies for these diseases.

This research was reported in the January 18 Proceedings of the National Academy of Sciences.