Turmeric ingredient makes membranes behave for better health

March 10, 2009 Source: www.laleva.org

Revered in India as "holy powder," the marigold-colored spice known as turmeric has been used for centuries to treat wounds, infections and other health problems. In recent years, research into the healing powers of turmeric's main ingredient, curcumin, has burgeoned, as its astonishing array of antioxidant, anti-cancer, antibiotic, antiviral and other properties has been revealed.

 In ancient Hindu medicine, it was used to treat sprains and swelling. Modern medicine uncovered its anti-inflammatory and antioxidant properties, which have been used to treat everything from liver disorders and diabetic wounds to runny noses. Some bandage brands in India even contain turmeric as a disinfectant. Recently, scientists added another potential benefit to the list: preventing Alzheimer’s disease. Intrigued by the fact that the elderly population of India has one of the lowest rates of Alzheimer’s cases in the world, researchers at UCLA began looking at differences between the American and Indian diets and landed on turmeric. Turmeric, a staple in Indian cooking, is featured in curries, soups, and meat dishes. It’s as common in Indian cuisine as salt and pepper are in American cuisine. Bharat B. Aggarwal, a senior cancer researcher at M.D. Anderson Cancer Center in Houston, says the average Indian eats turmeric at every meal—about a gram a day. The UCLA group hypothesized that curcumin, a chemical in turmeric, might clean up or block the buildup of amyloid plaques, which scientists believe may contribute to Alzheimer’s.

The researchers began clinical trials of turmeric’s effect on the disease in 2004, and the results were astounding. In the first studies with mice, the amyloid plaques decreased by roughly 50 percent in those fed low doses of curcumin-rich food. UCLA recently completed a similar study with humans, as did the Chinese University of Hong Kong. The Hong Kong trial demonstrated that curcumin has no adverse side effects (unlike many Alzheimer’s drugs, which can cause gastrointestinal problems). They tested a range of doses and found that a high dose was not any more effective than doses as low as 1 gram. Because they weren’t able to look directly at the Alzheimer’s patients’ brains, the researchers had difficulty measuring curcumin’s effectiveness on amyloid plaques; however, they did find more amyloid proteins in the patients’ blood, suggesting that curcumin may have broken down some of the plaques.

Most interestingly, in UCLA’s human trial, Alzheimer’s patients were given high doses of curcumin in a supplement, and yet none of the chemical was absorbed. The researchers now believe that curcumin must first be dissolved through cooking in fat in order to be effective on the Alzheimer’s brain. This likely explains India’s low rate of Alzheimer’s, and it also accounts for curcumin’s success in mice that ate it in their food. According to UCLA researcher Sally Frautschy, this is why people should cook with turmeric rather than take supplements. However, researchers all over the country are having trouble getting funding for future trials, says Frautschy, even though this data strongly suggests that Alzheimer’s may be mostly preventable.

Future studies are needed to pinpoint the exact amount of turmeric that’s effective in fighting Alzheimer’s, but if you want to increase your curcumin intake in the meantime, it can’t hurt to try some new turmeric-rich recipes. Turmeric, whether used as fresh root or as dry powder, contains 5 percent curcumin. Studies have shown that turmeric from Curcuma Longa plants in Southeast Asia contain more curcumin than turmeric found in the plants of East Asia.

Yet little has been known about exactly how curcumin works inside the body.

Now, University of Michigan researchers led by Ayyalusamy Ramamoorthy have discovered that curcumin acts as a disciplinarian, inserting itself into cell membranes and making them more orderly, a move that improves cells' resistance to infection and malignancy.

"The membrane goes from being crazy and floppy to being more disciplined and ordered, so that information flow through it can be controlled," said Ramamoorthy, a professor of chemistry and biophysics. The findings were published online March 3 in the Journal of the American Chemical Society.

The research project melds Ramamoorthy's past with his current scientific interests. As a child in India, he was given turmeric-laced milk to drink when he had a cold, and he breathed steam infused with turmeric to relieve congestion. Now as researcher he is fascinated with proteins that are associated with biological membranes, and he uses a technique called solid-state NMR spectroscopy to reveal atom-level details of these important molecules and the membranous milieu in which they operate.

"Probing high-resolution intermolecular interactions in the messy membrane environment has been a major challenge to commonly-used biophysical techniques," Ramamoorthy said. His research group recently developed the two-dimensional solid-state NMR technique that they used to probe curcumin-membrane communication in this study.

Scientists have speculated that curcumin does its health-promoting work by interacting directly with membrane proteins, but the U-M findings challenge that notion. Instead, the researchers found that curcumin regulates the action of membrane proteins indirectly, by changing the physical properties of the membrane.

Ramamoorthy's group now is collaborating with chemistry professor Masato Koreeda and U-M Life Sciences Institute researcher Jason Gestwicki to study a variety of curcumin derivatives, some of which have enhanced potency. "We want to see how these various derivatives interact with the membrane, to see if the interactions are the same as what we have observed in the current study," Ramamoorthy said. "Such a comparative study could lead to the development of potent compounds to treat infection and other diseases."

In a related line of research, Ramamoorthy's team is using the same methods to investigate the effects of curcumin on the formation of amyloids---clumps of fibrous protein believed to be involved in type 2 diabetes, Alzheimer's disease, Parkinson's disease, and many other maladies. In addition, the researchers are looking to see whether other natural products, such as polyphenols (compounds found in many plant foods that are known to have antioxidant properties) and capsaicin (a pain reliever derived from hot peppers), interact with membranes in the same way as curcumin.

More information: Journal of the American Chemical Society: http://pubs.acs.org/journal/jacsat 

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