Gorilla Staple Adds Spice to New Drugs

By Cheryl Lyn Dybas
Special to The Washington Post
Monday, November 27, 2006

NEW BRUNSWICK, N.J. -- A clear vial filled with amber fluid rests on scientist Ilya Raskin's desk, glinting in the autumn sunlight streaming through his office window. The container, a small glass bottle with a plain white screw-top, contains a substance Raskin calls 006. "Double-zero-six" is potentially more precious than the rarest topaz.

Raskin is a biochemist at Rutgers University's Biotechnology Center. The golden liquid on his desk may prove to be one of the most powerful anti-inflammatory substances ever discovered. "It contains a derivative of a plant known as grains of paradise, or Aframomum melegueta, a member of the ginger family," said Raskin. The compound works in a similar way to the well-known anti-inflammatory drugs Vioxx, Celebrex and Bextra but, it is hoped, without their side effects, said Raskin and other scientists.

Aframomum is not easy to come by. It grows in just one place: the vine-choked swampy lowlands of West Africa's Grain Coast. Stretching from Sherbro Island in Sierra Leone to Cape Palmas in Liberia, this rain-drenched, humid land is named for its abundant grains of paradise.

Outside Africa, Aframomum is usually available only as a hard-to-find spice. For their experiments, Raskin and colleagues hire African botanists to inspect the seeds and ship them to the United States.

Raskin first became interested in Aframomum during an international effort to search for medicines from plants. "Aframomum contains compounds called gingerols, which are chemically similar to other anti-inflammatory compounds," he said. "That's what initially drew our attention to the plant, and was confirmed in the lab."

Plant-derived drugs are hardly new: aspirin, for example, is a synthetic version of a natural substance found in willow bark, and the heart medication digitalis is made from the foxglove plant.

Humans may not be the only creatures that use Aframomum to treat inflammation and infection, said primatologist Michael Huffman of Kyoto University's Primate Research Institute in Japan. He said studies have shown that Western lowland gorillas in Africa prefer Aframomum shoots and seedpods to other foods.

In zoos, the absence of Aframomum and other African plants in the feed given to captive Western lowland gorillas may be a factor in an unexplained heart condition many have developed, say Ellen Dierenfeld, staff nutritionist of the St. Louis Zoo, and Melissa Remis, a primatologist at Purdue University.

"Western lowland gorillas in captivity aren't fed African plants," Dierenfeld said. "We need to look very closely at this aspect of their health to see if there's a link among diet, inflammation or infection, and heart disease."

For humans afflicted with inflammatory diseases, scientists are taking their cue from native African healers, who have used Aframomum for centuries to treat infections of all kinds, said biochemist Christopher Okunji of the National Institute of Allergy and Infectious Diseases.

"In the West African culture in which I was raised," Okunji said, "Aframomum is an important part of daily life. For example, when a visitor arrives at someone's home, no discussion begins until all partake of Aframomum seeds. People far back in African history likely knew that Aframomum was a good thing to eat if you didn't want to get sick."

Okunji's research has shown that one species of Aframomum has significant antimicrobial activity in laboratory tests. In a published study involving cell cultures, Okunji showed that the plant works against the microbe responsible for a hard-to-treat infection, methicillin-resistant Staphylococcus aureus. MRSA, which has reached epidemic levels in some hospitals and other confined places, is impervious to every penicillin-like antibiotic now available.

Okunji has conducted research at Raskin's lab, where lucky visitors may leave with their own thimble-size jar of bronze liquid and a pinch of Aframomum seeds, from which "006" is derived.

"If you spread a thin layer of this substance on a paper-cut or an aching joint," said scientist Neb Ilic of Phytomedics Inc., a pharmaceutical company in Jamesburg, N.J., "there's a warm sensation for a brief time, then the inflammation disappears."

Ilic is a visiting scientist at Rutgers, which has patents pending on Aframomum-related discoveries. Rutgers has licensed those rights to Phytomedics, Raskin said.

Phytomedics has licensed cosmetic-only rights to Avon Products Inc. to manufacture skin-care products that contain Aframomum, said Tolo Fridlender, president of Phytomedics.

Avon scientist Xiaochun Luo said the cosmetic's development is based on what Luo calls Aframomum's superior ability to counteract skin irritation. Avon expects to release the products next spring or summer.

Phytomedics is not alone in its quest to market Aframomum. Another group of researchers, headed by Kenneth Kornman, president and chief scientific officer of Interleukin Genetics Inc., in Waltham, Mass., also has a patent pending on Aframomum applications. Kornman and partners in Interleukin Genetics conducted a clinical trial in humans, completed last summer, of Aframomum's ability to inhibit a component of the immune system known as cytokine modulators.

Cytokine modulators regulate inflammatory responses, which Interleukin Genetics attempted to slow down in its clinical trial. Based on early results, which the company is just beginning to review, said Kornman, "Aframomum might successfully be used to treat diseases with inflammation as their hallmarks, like cardiovascular conditions, arthritis, osteoporosis and Alzheimer's disease."

The clinical trial included blood tests for markers of inflammation, such as C-reactive protein, in volunteers treated with Aframomum or substances from other plants -- blueberry, blackberry and rose hips.

"Although it's too early to say for sure which plant had the most effect, inflammatory markers in people in the Aframomum group responded differently," said Kornman.

In earlier tests in cell cultures, Aframomum "at a very low concentration significantly inhibited the production of C-reactive protein," he said.

If Aframomum lives up to the current hopes for it, Okunji said, "we will owe a great debt to early native healers in Africa" -- and the wild lowland gorillas whose habits they perhaps observed and mimicked.

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