New Medicines From Old Crops

by James A. Duke, Economic Botanist, ARS, USDA, Beltsville, MD, and James D. McChesney, Director, Research Institute of Pharmaceutical Sciences, University of Mississippi, Oxford.

Columbus set sail 500 years ago, seeking black peppers and Asian Indians. Instead, he found red peppers and American Indians and changed the cuisines of the world. Red pepper has become the world's leading spice, used in hot cuisine from Bombay to Bangkok, Karachi to Kunming, and Sao Tome to Szechwan. It is even considered the national spice of Ethiopia. Interestingly, the compound that gives red pepper its pungency also gives it some medicinal potential.

Today, there is much interest in designing foods that can reduce the probability of diseases like cancer; they are sometimes called "designer foods," "food farmacy," "nutriceuticals," or "prandial pseudoprescriptions." Hundreds of bioactive compounds in our food crops have indicated healthful activities. A computer data base at the University of Illinois (Chicago) enumerates dozens of compounds in the peppers (Capsicum spp.) reported to be cancer-preventive, or antitumor compounds. Most of the compounds are rather common and can be found in many crops.

However, USDA does not encourage self-diagnosis or self-treatment with herbal medication. Despite their history as folk medicines, many of these compounds are still in need of much more clinical research. Many of these properties are not yet proven to the standards of the U.S. Food and Drug Administration.

Cancer is one of the most feared diseases in the United States, although coronary disease is the biggest killer. Because of the low incidence of stomach cancer in Latin America, where aji (Capsicum spp.) is the leading spice, it has been suggested that aji may prevent stomach cancer. Antioxidants (compounds that prevent the oxidative damage of free radicals) like capsaicin seem to prevent cancer, at least in experimental animals, by nullifying the cancer-causing activities of nitrosamines and other carcinogens.

Strangely, hot (pungent) compounds, once thought to cause ulcers, are among those showing signs of ulcer-preventive activities. And it is the hot compounds (capsaicin in hot peppers; a sulfur-containing compound in garlic and onion; gingerols in ginger; and isothiocyanates in conventional crops like mustards and onions) that may offer some cancer-preventive activities as well. capsaicin is just one of several antioxidants in Capsicum. Antioxidants are believed to help reduce the incidence of heart disease and cancer as well as several other, more minor maladies like cataracts and some autoimmune diseases such as arthritis.

Ajo, or garlic (Album sativum), may be the second leading spice in Latin America. Both onion and garlic contain interesting compounds (such as the compound ajoene) that reduce the tendency of blood to clot and somewhat improve one's odds against arteriosclerosis and heart attack. Aspirin is already recognized by the medical profession in this regard. Others also suggest that several of the compounds in onion and garlic (and also limonene from citrus) prevent cancer. Would North America be better off adopting a salad dressing containing capsicum, garlic, and lemon juice? This recipe contains several compounds claimed to reduce the incidence of heart failure and cancer.

Capsaicin

Like garlic, ginger, and many of our conventional crops, red pepper has worked its way from the spice rack to the medicine chest. Capsaicin, the major active ingredient in red pepper, is now found in legitimate medications for such things as arthritis and herpes zoster (also called shingles). The many biological activities of capsaicin may be described as analgesic, anaphylactic, anesthetic, antiaggregant, anti-inflammatory, antineuralgic, antinociceptive, antioxidant, antiulcer, cancer-preventive, carcinogenic, cardiotonic, cyclo-oxygenase-inhibitory, diaphoretic, hypothermic, irritant, 5- lipoxygenase- inhibitory, neurotoxic, repellant, respirosensitizing, and sialogogue. Some of these reported activities are good, and some are bad. As with synthetic drugs, most (if not all) natural drugs have side effects and can be toxic in high doses.

Garlic contains interesting compounds that reduce the tendency for blood to clot and somewhat improve one's odds against heart attack. Ken Hammond/USDA 92BW0825-14

Red pepper has worked its way from the spice rack to the medicine chest. Capsaicin the major active ingredient in red pepper, is now found in legitimate medications for such things as arthritis and shingles. Ken Hammond/USDA 92BW0840-11A

Capsaicin is rarely found outside the hot pepper family. Used in South America as an anodyne (painkiller) for centuries, peppers more recently have yielded their capsaicin to therapeutic painkiller preparations such as Axsaine and Zostrix. Of the 20 percent of shingles sufferers who experience postherpetic nerve pain, 75 percent report less pain after using creams containing capsaicin.

At the Eppley Institute for Cancer Research (Nebraska), capsaicin is being studied for its potential to deplete substance P, a normal human body chemical that transmits pain messages from nerve endings in the skin to the central nervous system. Where it is applied, capsaicin inhibits the production of substance P. About 1 percent of the population suffers from cluster headache, and 80 percent of those persons are males. These patients reported dramatic relief when dilute capsaicin was applied to the nostril on the side where the cluster headache occurred, but not when applied to the other nostril. Further, capsaicin ointment prevented cluster headache when applied to the temples In the 19th century, the use of a drop or two of capsicum extract was recommended for toothache. The use of capsicum preparations was even recommended to prevent thumbsucking and nailbiting.

Capsaicin is known to inhibit pain-inducing inflammation (for example, in arthritis) by blocking the release of a substance called neurokinin, but it is not effective when taken orally. Capsaicin analogs (chemical compounds that differ structurally) were developed, which proved to be orally active anti-inflammatory analgesics. These work differently from the way conventional, nonsteroidal anti-inflammatory drugs work. Capsaicin has thus functioned as a prototype in the development of a new approach to treat the inflammation of arthritis.

Steroids

Corticosteroids are also recommended for some cases of arthritis. Few Americans realize that steroids represent about 15 percent of modern medicinal prescriptions. The medicines loosely called steroids are widely used to treat arthritis, achieve contraception, etc. At first, steroids were obtained from animal urine. Then it was discovered that a compound called diosgenin, from yams (Dioscorea spp.), can be converted to steroids. A burgeoning industry of steroid contraceptives soon followed. Gradually, however, wild yams became more and more unpredictable as steroid sources. Today, most steroids are made from natural compounds called sitosterol and stigmasterol, byproducts of soybean processing. Assuming that the world pharmaceutical market has a value of $150 billion and that steroids capture 15 percent of that market, the soy byproducts called steroids are worth more than $20 billion in their final pharmaceutical form. This is a significant example of adding value by processing, since the byproducts themselves are relatively low-cost.