Plants can not run away from their enemies nor get rid of troublesome pests as humans or other animals do, so what have they evolved to protect themselves? Whatever this protection is it must be successful, for the diversity and richness of green plants is extraordinary, and their dominance in most ecosystems of the world is unquestioned. Plant successes are closely intertwined with the evolution and production of highly diverse compounds known as secondary metabolites, compounds that are not essential for growth and reproduction, but rather, through interaction with their environment, enhance plant prospects of survival. These metabolites are therefore plant agents for chemical warfare, allowing plants to ward off microorganisms, insects, and other animals acting as predators and pathogens . Such compounds may also be valuable to humans for the same purposes, and therefore may be used as medicines.
What Characterizes Medicinal Plants
There are twenty thousand known secondary plant metabolites, all exhibiting a remarkable array of organic compounds that clearly provide a selective advantage to the producer, which outweighs their cost of production. Humans benefit from their production by using many of them for medicinal purposes to fight infections and diseases. An estimated two-fifths of all modern pharmaceutical products in the United States contain one or more naturally derived ingredients, the majority of which are secondary metabolites, such as alkaloids, glycosides, terpenes, steroids, and other classes grouped according to their physiological activity in humans or chemical structure. To illustrate the breadth of human reliance on medicinal plants, the accompanying table provides a list of the most significant plants, their uses in modern medicine, and the major secondary metabolites responsible for their activities. This list grows annually as new plants are found with desired activities and remedies to become pharmaceuticals for use in medicine.
|COMMON MEDICINAL PLANTS AND THEIR USES|
|Scientific Name||Common Name||Family||Compounds||Compound Class||Uses|
|Atropa belladonna, Duboisia myoporoides||Belladonna||Solanaceae||Atropine, scopolamine||Alkaloid||Anticholinergic, motion sickness, mydriatic|
|Cassia/Senna species||Senna||Fabaceae||Sennoside||Glycoside, anthraquinone||Laxative|
|Catharanthus roseus||Madagascar periwinkle||Apocynaceae||Vincristine, vinblastine||Alkaloid||Anticancer (antileukemia)|
|Chondrodendron tomentosa, Curarea toxicofera||Curare||Menispermaceae||(+)-Tubocurarine||Alkaloid||Reversible muscle relaxant|
|Cinchona calisaya, Cinchona officinalis||Jesuits' bark||Rubiaceae||Quinine, quinidine||Alkaloid||Antimalaria (quinine), antiarrhythmia (quinidine)|
|Colchicum autumnale||Autumn crocus||Liliaceae||Colchicine||Alkaloid||Gout|
|Digitalis lanata, Digitalis purpurea||Foxglove||Scrophulariaceae||Digoxin, digitoxin, lanatosides||Cardiac glycoside (steroidal)||Heart failure and irregularity|
|Dioscorea species||Yam||Dioscoreaceae||Diosgenin, precursor of human hormones and cortisone||Saponin glycoside (steroidal)||Female oral contraceptives, topical creams|
|Ephedra sinica||Ephedra, Ma huang||Ephedraceae||Ephedrine||Alkaloid||Bronchodilator, stimulant|
|Podophyllum peltatum||May-apple||Berberidaceae||Podophyllotoxin, etoposide||Resin||Anticancer|
|Rauwolfia serpentina||Apocynaceae||Reserpine||Alkaloid||Antihypertensive, tranquilizer|
|Taxus brevifolia||Pacific yew||Taxaceae||Taxol||Diterpene||Anticancer (ovarian, breast)|
How Plant Pharmaceuticals Are Discovered
The search for new pharmaceuticals from plants is possible using a number of distinct strategies. Random collecting of plants by field gathering is the simplest but least efficient way. The chances are much greater that new compounds of medicinal value will be discovered if there is some degree of selectivity employed by collecting those plants that a botanist knows are related to others already having useful or abundant classes of secondary metabolites. Even more relevant is to collect plants already targeted for specific medicinal purposes, possibly among indigenous or ethnic peoples who use traditional, plant-derived medicines often with great success to provide for their well-being. Such data are part of ethnobotany , when researchers often obtain detailed information on the plants people use to treat illnesses, such as the species, specific disease being treated, plant part preferred, and how that part is prepared and used for treatment. This strategy can provide rapid access to plants already identified by traditional practitioners as having value for curing diseases, and this shortcut often sets the researcher rapidly on the road to the discovery of new drugs.
Taking the ethnobotanical approach, a specific part of the targeted ethnomedicinal plant is extracted, usually in a solvent like ethanol, and then studied in biodirected assays or tests to determine its value using, for instance, tissue cultured cells impregnated with the organism known to cause the disease. For example, to assay for malaria the procedure could involve culturing red blood cells infected with the malarial-causing protozoan Plasmodium falciparum, placing a few drops of extract into the culture, and examining after a few days what effect, if any, the addition of the extract had on the protozoa. One final step in this process leading to the discovery of a new drug is to establish the mechanism of action of the compound, reactions in the body, and side effects or toxicity of taking it. The whole process from field discovery to a new pharmaceutical takes up to ten years and requires a multidisciplinary-interactive approach involving ethnobotanists , natural products chemists, pharmacognosists (those who study the biochemistry of natural products), and cell and molecular biologists.
Medically Important Compounds Derived From Plants
About ninety species of plants contribute the most important drugs currently used globally, and of these about 75 percent have the same or related uses as the plant from which each was discovered. Two examples provide additional details of their discovery and development as drugs.
Eastern North American Indians long used the roots and rhizomes (underground stems) of the native May-apple (Podophyllum peltatum, Berberidaceae) as a drastic laxative. By the nineteenth century, white "Indian Doctors" used extracts of these parts to treat cancerous tumors and skin ulcers, perhaps learned from Indians or by direct observation of its corrosive and irritating nature. The plant's main secondary metabolite is podophyllotoxin, a resin responsible for May-apple's antitumor effects. It is a mitotic poison that inhibits cell division and thus prevents unregulated growth leading to cancerous cells and tumors. However, in clinical trials podophyllotoxin proved too toxic for use as a cancer chemotherapeutic agent, although it remains the drug of choice as a caustic in removing venereal warts and other benign tumors.
Attempts to find safer compounds led chemists to manipulate the molecule, and by trial and error they discovered a semisynthetic derivative that proved at least as effective as the original compound without the same level of toxicity. (Semisynthetics are products of chemical manipulation using the naturally occurring plant compound as a base.) A compound called etopo-side was eventually found most valuable in treating a type (non-small cell) of lung cancer, testicular cancer, and lymphomas (cancer of lymphoid tissue), and particular (monocytic) leukemias (cancer of blood-forming organs) by preventing target cells from entering cell division. Etoposide was approved for use in the United States in 1983, twelve years after its discovery. Peak annual sales of the compound reached approximately $300 million in the late 1980s and early 1990s, and thousands of lives have been prolonged or saved during nearly two decades of its use as a leading anticancer drug derived from plants. It is possibly the most important pharmaceutical originating from a plant species native to eastern North America.
Heart and vascular disease is the number one killer in the United States, a position held virtually every year in the twentieth century. Fluid accumulation or edema (dropsy) and subsequent congestive heart failure have been treated by European farmers and housewives as part of European folk medicine for a long time. Their remedy consisted of a concoction of numerous herbs that always contained leaves of foxglove (Digitalis species, Scrophulariaceae). In the 1700s William Withering, an English botanist and physician, observed in the countryside the successful use of this herbal mixture to treat dropsy and associated diseases. He eventually selected one plant from the mixture as the probable source of activity, and in 1785 Withering published his landmark book An Account of the Foxglove, and Some of Its Medicinal Uses in which he described how to determine the correct dosage (for foxglove was considered a potent poison that was ineffective medicinally unless used at near toxic levels) and how to prepare fox-glove, favoring the use of powdered leaves.
Withering's discovery revolutionized therapy associated with heart and vascular disease, and even today, powdered foxglove leaves are still prescribed and used much as they were more than two centuries ago. The active leaf metabolites are cardiotonic glycosides obtained mostly from two European species, Digitalis lanata and D. purpurea. They provide the most widely used compounds, digoxin (also available synthetically), digitoxin, and lanatosides. The magnitude of the need for cardiotonic therapy is suggested by the estimate that more than three million cardiac sufferers in the United States routinely use the preferred digoxin as one of several available drugs.
In congestive heart failure, the heart does not function adequately as a blood pump, giving rise to either congestion of blood in the lungs or backup pressure of blood in the veins leading to the heart. When the veins become engorged, fluid accumulates in the tissues, and the swelling is known as edema or dropsy. Cardiotonic glycosides increase the force of heart muscle contraction without a concomitant increase in oxygen consumption. The heart muscle thus becomes a more efficient pump and is better able to meet the demands of the circulatory system. If heart failure is brought on by high blood pressure or hardening (loss of elasticity) of the arteries, cardiotonic glycosides are also widely used to increase contractibility and improve the tone of the heart muscle, resulting in a slower but much stronger heart beat. If the heart begins to beat irregularity, again these cardioactive compounds will convert irregularities and rapid rates to normal rhythm and rate.
The search for new medicinal plants continues as remote regions of natural habitat are explored by botanists, plant systematists , and ethnobotanists. Further clinical studies of chemical components of these new discoveries may yield important novel drugs for the treatment of human diseases.
see also Alkaloids; Cannabis; Coca; Dioscorea; Economic Importance of Plants; Ethnobotany; Herbals and Herbalists; Opium Poppy; Pharmaceutical Scientist; Plant Prospecting; Psychoactive Plants; Systematics, Plant.
Walter H. Lewis
Balick, Michael J., and Paul Alan Cox. Plants, People, and Culture: The Science of Ethnobotany. New York: Scientific American Library, 1996.
Kreig, Margaret G. Green Medicine. New York: Rand McNally, 1964.
Lewis, Walter H., and Memory P. F. Elvin-Lewis. Medical Botany: Plants Affecting Man's Health. New York: John Wiley & Sons, 1977.
Nigg, Herbert N., and David Seigler, eds. Phytochemical Resources for Medicine and Agriculture. New York: Plenum Press, 1992.
Plotkin, Mark. Tales of a Shaman's Apprentice. New York: Viking, 1993.
Robbers, James E., and Varro E. Tyler. Tyler's Herbs of Choice: The Therapeutic Use of Phytochemicals. Binghamton, NY: Haworth Herbal Press, 1998.
Upon their arrival in what is today Latin America, European conquerors found an impressive array of healing plants used by the natives. Accompanying the conquerors were missionaries and occasionally a physician, and it is from their chronicles that we know about medicinal plants of pre-Conquest America. Among them, the accounts of Father Bernardino de Sahagún and especially those of the physician Francisco Hernández in Mexico describe a large number of medicinal plants used by the peoples of Mesoamerica in the sixteenth century. These accounts, however, cover only a fraction of the plants actually used, their applications, and mode of use, since medicine men were understandably reluctant to reveal the secrets of their healing plants to the invaders.
Medicine men and women were involved not only in healing individual patients but also in maintaining the integrity of their community. Their highly sophisticated knowledge of healing plants came from years of apprenticeship in well-established traditions and a lifetime of practice that included familiarity with healing plants, their habitats, their effects and interactions; their remedies almost always used plants in combination. During some healing rituals, medicine men consumed hallucinogenic plants. Considered magical and the quintessential medicine, hallucinogenic plants were used as guides to find the causes of challenging illnesses and to foresee events. Christian missionaries labeled these practices diabolic, and medicine men and women were ruthlessly persecuted.
With the social disintegration of the conquered peoples in the fifteenth and sixteenth centuries and the severe disruption of healing traditions, untold knowledge of medicinal plants was lost. However, because of their highly effective cures, native herbalists were eagerly sought after during colonial and postcolonial times. After the Conquest, missionaries continued using and recording the properties of medicinal plants; the religious orders that followed profited from their trade. Nonetheless, most plants considered magical or sacred by the natives were banished as instruments of the devil. Native classifications of plants such as "male" or "female" were replaced by concepts such as "hot" or "cold," which were then prevalent in European medicine. Healing plants of European, African, and Asian origin were added to the colonial pharmacopoeia; some were readily adopted by native herbalists.
Plants gained or lost favor according to economic and social circumstances. A few examples illustrate this point. In 1569, the writings of the Spanish physician Nicolás Monardes popularized many American medicinal plants in Europe; of these plants, balsam of Peru, the resin from the tree Myroxylon balsamum, became a worldwide treatment for wounds, infections, and skin ailments and was used as incense by the Roman Catholic Church (for both ritual and fumigatory purposes). The Pacific coast of El Salvador was the most important producer. Since the advent of antibiotics in the 1930s, the economic importance of this plant diminished considerably.
A different fate befell the forest vines of special species of Chondrodendron, used as traditional ingredients of curare, the powerful arrow poison from the Amazon that produces muscle paralysis. One of the active chemicals of curare, tubocuraine, is medically used to reduce convulsions caused by tetanus or electric-shock therapy and as a temporary muscle relaxant in some surgeries and in neu-ropathological spasms. Similarly, in Mesoamerica, the tubers of wild yams (certain species of Dioscorea), used since pre-Columbian times by women to control menstruation and for their soaplike suds, never received wide notice by colonial Europeans. Yet today, thanks to a discovery by a Japanese chemist in 1938, they are very important sources of steroidal sapogenins, from which pharmaceutical companies in Mexico synthesize corticosterol-based anti-inflammatories, androgens, estrogens, progesterones, and oral contraceptives. On the other hand, the barks of several species of Cinchona trees from the northern Andes, for which there is no evidence of use before the seventeenth century, became extremely important antimalarial drugs from then onward, thereby making European colonial expansion to the world's tropics more feasible. They are today the source of quinine and its derivatives and are also used to treat hemorrhoids, varicose veins, and cardiac arrhythmias.
Mention must be made of two "medicine" plants held in the highest esteem during pre-Columbian times: the first, coca (several species of Erythroxylon), cultivated from Bolivia and Brazil to Nicaragua, was almost universally considered a sacred plant. Restricted to men and, among the Incas, to athletes, message runners, and the nobility, the partaking of the leaves for chewing was a highly ritualized social occasion. Its effect was mostly to suppress tiredness and hunger. Some missionaries disapproved of coca, and in the early 1600s the Inquisition bitterly condemned its use. By that time, however, several religious orders were profiting handsomely from coca production and trade, and their members frequently chewed the leaves. After silver was discovered in Peru in the mid-1500s, enormous quantities of coca were brought in to keep the Indian forced laborers in the mines from feeling tired or hungry. Coca became an important commercial crop in colonial Peru and Ecuador. Cocaine, one of the many alkaloids present in coca, was first isolated in 1858; today, several compounds derived from cocaine are important anesthetics. Cocaine is also used as a recreational drug because of its euphoric and stimulant properties. Unfortunately, cocaine consumption is erroneously confused with traditional coca chewing, a very different activity both socially and physiologically. Recreational cocaine is today an illegal drug; its trade, fueled by a seemingly insatiable demand in the United States and in Europe, has brought grave social and political disruptions to Colombia, Peru, Bolivia, and other Latin American countries.
The second plant, tobacco (Nicotiana tabacum), was considered a powerful protector of medicine men and warriors, who drank infusions of the leaves, applied them to their bodies, or inhaled smoke from burned leaves. Tobacco was a common component of the hallucinogenic mixtures prepared by medicine men for diagnosis and divination. It also had more mundane uses: to relieve headaches, to cure skin infections, to heal wounds, to kill and repel insects. With the social disruption following the Spanish Conquest, tobacco use was no longer restricted, and the conquered men and women took to inhaling its smoke to soothe their distress. Christian priests at first disapproved of this practice, then took it up themselves; African slaves readily followed.
Tobacco was introduced to Europe in the sixteenth century as a sedative, especially for painful illnesses, but soon its narcotic properties and the novelty of "drinking smoke" or snuffing the powdered leaves turned it into a recreational substance favored by European intellectuals and the colonial elites. Indians, however, continued using tobacco mostly as a medicine; their gardens invariably included a few tobacco plants. Because of the demand, tobacco production was rapidly commercialized, and its preparation and use were standardized. By the seventeenth century, some areas of the colonies, especially in Cuba, Trinidad, and Venezuela, had been selected for production. In those areas, "industrial" cultivation was associated with large-scale hacienda systems and African slave labor; elsewhere, tobacco growing was commonly in the hands of small landholders, poor peasants, and runaway slaves. Eventually, small tobacco growers became important in the popular uprisings that led to independence from Spain. Today, the medicinal properties of tobacco are virtually unknown, and its use is mostly as a legal recreational narcotic.
Advances in chemistry during the late eighteenth century and through the nineteenth century led to the extraction and purification of physiologically active compounds from medicinal plants, allowing medical doctors better control of the effects of their prescriptions and permitting the establishment of a pharmaceutical industry. European countries, interested in learning about plant resources that might yield economic benefits, sponsored systematic searches of the American flora through scientific expeditions. In the late eighteenth century, the explorations of Alexander von Humboldt and José Celestino Mutis enriched knowledge about medicinal plants in the upper Amazon basin and northern Andes, as did Richard Spruce's reports in the nineteenth century. In the twentieth century, scientific explorations intensified, involving universities and government agencies in various countries and resulting in improved botanical and pharmacological information.
In the 1930s, with the advent of antibiotics—called "miracle drugs"—the prestige of skillfully marketed synthetic drugs started to eclipse the importance of medicinal plants, and for several decades the latter were considered less reliable agents of healing; since the 1970s, however, pathogens resistant to antibiotics have evolved, and evidence has accumulated of toxic secondary effects and improper use of pharmaceutical products that cause severe health problems. For these reasons, and also because of the prohibitive cost of synthetic drugs to large segments of the Latin American population, some governments have started programs studying their medicinal herbal lore, especially in countries where large Indian populations have kept the herbal tradition alive. Mexico, for example, has produced several government publications on its medicinal flora, and Bolivia has developed successful programs integrating the biomedical traditions of Western medicine with ethnomedical systems such as those of the highly reputed Kallawaya herbal healers.
Pharmaceutical companies continue to send scientific expeditions to Latin America in search of pharmacologically useful plants. A major debate today concerns whether these European and U.S. companies can have exclusive patent rights—and access to potentially high profits—for synthetic drugs developed from plants found on Latin American soils.
An outstanding source of historical material about Latin American medicinal plants is Victor Manuel Patiño, Plantas cultivadas y animales domésticos en América equinoccial. Vol. 3, Fibras, medicinas, misceláneas (1967). Excellent information about the best-known medicinal plants, including pharmacological and historical aspects of some Latin American natives, is given in Julia Morton, Major Medicinal Plants: Botany, Culture, and Uses (1977). Regional reference material can be found for Mexico in Maximino Martínez, Las plantas medicinales de México (1990); and Xavier Lozoya L., Flora medicinal de México (1982). For the Amazon forest, see Richard Schultes, The Healing Forest: Medicinal and Toxic Plants of the Northwest Amazonia (1990); for Colombia, consult Hernando García Barriga, Flora medicinal de Colombia (1974); for the mid-Andean region, especially Bolivia, see Joseph Bastien, Healers of the Andes: Kallawaya Herbalists and Their Medicinal Plants (1987). On specific plants, Cultural Survival Report 23, "Coca and Cocaine—Effects on People and Policy in Latin America" (1985).
Campos-Costero, Isaac. "Marijuana, Madness, and Modernity in Global Mexico, 1545–1920." Ph.D. diss., Harvard University, 2006.
Ortiz Echániz, Silvia. La medicina tradicional en el norte de México. México, D.F.: Instituto Nacional de Antropología e Historia, 1999.
Montañez Anaya, Alfred. Utilización de plantas medicinales en el chamanismo como cultura amazónica. Florencia, Caquetá [Colombia]: Fondo Mixto para la Promoción de la Cultura y las Artes, 1997.
Mors, Walter B., Carlos Toledo Rizzini, Nuno Alvares Pereira, and Robert A. DeFilipps. Medicinal Plants of Brazil. Medicinal Plants of the World, 6. Algonac, MI: Reference Publications, 2000.
Stasi, Luiz Claudio di, and Clélia Akiko Hiruma-Lima. Plantas medicinais na Amazônia e na Mata Atlântica. São Paulo, SP: Editora UNESP, 2002.
Carmenza Olaya Fonstad