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See Inside February 2007

Spice Healer

An ingredient in curry shows promise for treating Alzheimer's, cancer and other diseases
TURMERIC



DANIELA NAOMI MOLNAR

Searching for new drugs by milling through ancient folk pharmacopoeia or by just picking a plant while walking in the woods has a decidedly checkered history. Many well-established therapeutic compounds originated in trees, shrubs, mollusks, even dirt. Aspirin came from willow bark, cholesterol-lowering statins from a mold, and the antimalarial artemisinin from a shrub used in traditional Chinese medicine. Yet after raising $90 million during the 1990s in a much publicized bid to tap indigenous knowledge for new drug leads, Shaman Pharmaceuticals had to lower its sights until it was doing nothing more than selling its products as nutritional supplements before finally shutting its doors for good a few years ago.

Now the trend may be reversing itself again. Recently a number of natural compounds--such as resveratrol from red wine and omega-3 fatty acids from fish oil--have begun to receive close scrutiny because preliminary research suggests they might treat and prevent disease inexpensively with few side effects. Turmeric, an orange-yellow powder from an Asian plant, Curcuma longa, has joined this list. No longer is it just an ingredient in vindaloos and tandooris that, since ancient times, has flavored food and prevented spoilage.

A chapter in a forthcoming book, for instance, describes the biologically active components of turmeric--curcumin and related compounds called curcuminoids--as having antioxidant, anti-inflammatory, antiviral, antibacterial and antifungal properties, with potential activity against cancer, diabetes, arthritis, Alzheimer's disease and other chronic maladies. And in 2005 nearly 300 scientific and technical papers referenced curcumin in the National Library of Medicine's PubMed database, compared with about 100 just five years earlier.

Scientists who sometimes jokingly label themselves curcuminologists are drawn to the compound both because of its many possible valuable effects in the body and its apparent low toxicity. They ponder how the spice or its derivatives might be used, not just as a treatment but as a low-cost preventive medication for some of the most feared ailments. As a treatment, it also has some enticing attributes. Because curcumin targets so many biological pathways, it could have benefits for cancer therapy: malignant cells may be slow to acquire resistance to it and so might have to go through multiple mutations to avoid the substance's multipronged attack.

But is the compound ready for widespread use? Some work offers grounds for caution. Among the more than 1,700 references to curcumin in PubMed are studies showing how a compound that can affect so many biological pathways can sometimes hit the wrong switch and actually help to foster disease.

Long Medical History
Known as HALDI in HINDI, jiang huang in Chinese, manjal in Tamil (and just plain "yuk" as the yellow stain on a white T-shirt from the splatting of ballpark mustard), turmeric has a medicinal history that dates back 5,000 years. At that time it was a key medicament for wound healing, blood cleansing and stomach ailments in India's Ayurvedic system of medicine.

The first record in PubMed of research on the biological activity of curcumin dates back to 1970, when a group of Indian researchers reported the effects of the compound on cholesterol levels in rats. The pace of studies picked up in the 1990s; one of the leaders was Bharat Aggarwal, a former scientist at Genentech who, before turning to curcumin, had taken another approach to seeking cancer treatments. That work led him circuitously to the compound.

In the 1980s Aggarwal and his team at Genentech were the first to purify two important immune molecules--tumor necrosis factor (TNF) alpha and beta--that have been identified as potential ?anticancer compounds. These molecules can, in fact, kill cancer cells when deployed in localized areas, but when circulated widely in the bloodstream, they take on different properties, acting as potent tumor promoters. The TNFs activate an important protein, nuclear factor kappa B (NF kappa B), which can then turn on a host of genes involved in inflammation and cell proliferation.

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