University of Michigan researchers led by Ayyalusamy Ramamoorthy now say 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, of findings that were published 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 say 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.
This research was supported by funding from the National Institutes of Health.
Article: Jeffrey Barry, Michelle Fritz, Jeffrey R. Brender, Pieter E. S. Smith, Dong-Kuk Lee† and Ayyalusamy Ramamoorthy, 'Determining the Effects of Lipophilic Drugs on Membrane Structure by Solid-State NMR Spectroscopy: The Case of the Antioxidant Curcumin', J. Am. Chem. Soc., Article ASAP Publication Date (Web): March 3, 2009 DOI: 10.1021/ja809217u
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