Solid state NMR has been used to help to explain why curcumin, one of the physiologically active components of the yellow spice turmeric has wound healing and other medicinal properties.

In work supported by the US National Institutes of Health, Ayyalusamy Ramamoorthy of the University of Michigan, together with undergraduates Jeffrey Barry and Michelle Fritz, post-doctoral fellow Jeffrey Brender, graduate student Pieter Smith and visiting professor from South Korea, Dong-Kuk Lee, have published details in the Journal of the American Chemical Society.

Turmeric, a member of the ginger family (Zingiberaceae), is revered in Indian cuisine and culture as a "holy powder". The marigold-coloured spice, with its unique and distinctive pungency, has been used not only in cooking but as a traditional pigment and medicine for centuries. It is commonly used to treat infections, help in wound healing, and other health problems.

More recently, however, biomedical researchers have demonstrated that the main active ingredient, curcumin, a polyphenolic compound has efficacy as an antioxidant, an anticancer agent, an antibiotic, and even an antiviral compound. While the lab chemistry of curcumin is well-known, it exists in two tautomeric forms, forms, for instance, the keto and enol, with the enol being more stable in the solid phase and in solution, little is yet known about exactly how curcumin behaves biochemically in the body.

Now, chemist and biophysicist Ramamoorthy, who specialises in cell membrane proteins, nanomedicine, and natural antibiotics, has pulled his expertise in these different fields together to reveal curcumin's disciplinarian mode of action. According to the team's findings, curcumin inserts itself into cell membranes and makes them behave in a more orderly manner, which the researchers suggest allows them to improve the 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," explains Ramamoorthy.

Ramamoorthy describes how 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 nasal congestion. Today, he is fascinated by the proteins that are associated with biological membranes and how small molecules affect and interact with these cell membrane proteins.

Membrane proteins act as catalysts, the enzymes, regulate the transport of nutrients and metabolites in and out of the cell, and are involved in intercellular communication, cell signalling.

Normally, one might turn to X-ray crystallography to get an atom-by-atom structure of a protein. Unfortunately, the majority cannot be crystallised easily and even those that can are rendered in an entirely unnatural state when removed from the membrane. Researchers would, nevertheless, like to understand the diverse functions of membrane proteins and to find ways to engineer their functionality for biomedical or biotechnological purposes. In this regard, high-resolution structure determinations are essential but so too are studies that reveal their dynamics.

Ramamoorthy and his colleagues have thus turned to the increasingly powerful technique of solid-state NMR spectroscopy to look closely at the behaviour and interactions of membrane proteins in their native state.

"Probing high-resolution intermolecular interactions in the messy membrane environment has been a major challenge to commonly-used biophysical techniques," Ramamoorthy says. He and his colleagues recently developed a novel two-dimensional solid-state NMR technique that they have now demonstrated in action by using it to probe the interaction between membrane and curcumin.

Previous research by others had hinted that the mode of action of curcumin in promoting health was due to direct interaction with membrane proteins. However, the Michigan team has shown this not to be the case. Instead, the researchers have demonstrated that curcumin regulates the action of membrane proteins indirectly, by changing the physical properties of the membrane itself.

Ramamoorthy's group now is collaborating with chemistry professor Masato Koreeda and Michigan's Life Sciences Institute researcher Professor Jason Gestwicki to study various chemically modified derivatives of curcumin to see whether they can enhance the potency of this compound. The researchers are also looking at other natural products, including capsaicin from hot peppers, which is a known analgesic, to reveal their mode of action in the light of the curcumin discovery.

"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 explains. "Such a comparative study could lead to the development of potent compounds to treat infection and other diseases."

Related links:

• J Am Chem Soc, 2009, in press
• Ramamoorthy Group

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.