Medicinal Plants

David S. Seigler
Department of Plant Biology
University of Illinois
Urbana, Illinois 61801 USA seigler@life.illinois.edu
http://www.life.illinois.edu/seigler

Outline: Medicinal Plants
Importance o “Primitive” cultures
+ Link to religion
+ Link to psychoactive drugs
Economics
Botanical o Many families

Chemical o Terpenes
+ Cardiac glycosides
+ Steroids
+ Metabolically altered triterpenes o Alkaloids
+ Analgesic drugs
+ Antitumor drugs
+ Emetics

o Anthraquinone glycosides
+ Laxatives o Polyketides
+ Aspirin o Mode of action
Herbal medicines

Reading
• CHAPTER 11, pp. 262 ff.

Introduction
• The use of medicinal plants is found in almost all cultures. In some, many types of plants are used. Some are efficacious and others are not.
• The science of botany originated in the study of medicinal plants. Chemistry, botany, and medicine were all considered one field until the 1700's.

Herbal medicines in Madagascar
Courtesy Dr. Voara Randrianasolo

Medicinal plants in Toluca market

• Many plant and fungal derivatives are important medicinally.
• The most important of the plant-derived compounds are terpenoids (such as steroids) and alkaloids.
• Substances such as anthraquinone glycosides as well as a variety of other types of glycosides are also widely used.

• These include the active principles of Salix
(Salicaceae), Artemisia cina (Asteraceae or
Compositae) (santonin used as an anthelmintic drug), quassia (used to control lice etc.).
• Table of some important medicinal plants on page 263.

• Presumably curative agents were discovered by trial and error.
• Sumerian drawings of opium from 2500 B.C. suggest that they were knowledgeable about medicinal plants.
• In 1770 B.C., from the Code of Hammurabi, a series of plants such as henbane
( Hyoscyamus niger , Solanaceae), licorice
( Glycyrrhiza sp., Fabaceae), and mints
(Mentha spp., Lamiaceae) were mentioned.

• The ancient Egyptians recorded much of their knowledge of plant drugs as well. Many of the plants used by them are still used in medicine.

The Greeks
• The Greeks made other significant contributions to medicine.
• The number of effective medicinal plants came to be about 300-400 species.
• Hippocrates (460-377 B.C.), Aristotle (384-
322 B.C.) and Theophrastus (372-287 B.C.) essentially started the science of botany.

Dioscorides
• The most significant contribution however, was Dioscorides (ca. 40-90 A.D.) He wrote a
5 volume work, De materia medica, that became the standard work for 1500 years.
• Because of later historical developments and the fact that Europe went into intellectual decline, the book was blindly followed and accepted without question until the fifteenth century.

Doctrine of Signatures
• Finally, a contemporary of da Vinci, Paracelsus
(1393-1451), broke publicly with the works of the
Greeks and advocated the "Doctrine of
Signatures". This was soon displaced by more objective methods.

• In the 19th century, such compounds as quinine, strychnine, morphine, and ephedrine were isolated and studied.
• Later (mostly in the twentieth century) many of the compounds were synthesized and some became available from that source.

• Most of the drugs used in western culture come from Europe and Asia, although a number of extremely important ones come from other sources.

Types of active compounds
• The most important types of compounds are terpenoids and alkaloids. Others such as fatty acids (e.g., chaulmoogra oil) are also used, however.
• The chemical structures of several important drug materials are given in this chapter.

Malaria and quinine
• Historically, malaria has been one of the worst of all human diseases.
• In some countries malaria is common and millions of people suffer from the disease throughout the world.
• Malaria is caused by a sporozoan of the genus Plasmodium and is passed from one human to another by mosquitoes.

• In the 17th century, Jesuits in South
America discovered that a native remedy for other diseases made from an infusion of the bark of cinchona
( Cinchona spp., Rubiaceae) coincidentally controlled malaria.

Peru in the early 1940s
Courtesy Dr. Walter Hodge

Quinine , Cinchona officinalis , Rubiaceae
Calisaya type
Courtesy Dr. Walter Hodge

Harvesting cinchona bark
Courtesy Dr. Walter Hodge

Courtesy Dr. Walter Hodge
Drying and storing cinchona bark

Types of Cinchona bark
Courtesy Dr. Walter Hodge

• The Dutch acquired seeds from a highyielding plant near Lake Titicaca, Bolivia.
After several years of trying to grow the plants and improve them, they were able to begin to cultivate high quality lines in the Dutch East
Indies and eventually they got a monopoly on the production of quinine.
• At the time of W.W. II, the allies were cut off from a supply of quinine.
• During the war, a number of synthetic substitutes for quinine were developed. Many are still important, but resistance to most is a major problem.

• Quinine is also used in small amounts to make tonic water and other soft drinks such as bitter lemon.
• Although there have been extensive searches for new plant-derived antimalarials, few have surfaced.
• One, artemisinin from Artemisia annua , has proven effective and is currently being used in southeast Asia.

Artemisia annua ,
Asteraceae or
Compositae

Ephedra or ma huang, Ephedra spp.,
Ephedraceae
• Infusions of Ephedra spp. (Ephedraceae, a gymnosperm) have been used for thousands of years in China. There it is often called "ma huang".
• In the 1920's the plant was "discovered" by western medicine and the active compounds isolated.

Ephedra, Ephedra sp., Ephedraceae

• Ephedrine and a series of related compounds are used today as decongestants (e.g., in Sudafed,
Robitussin etc.) and to treat low blood pressure.
• Most of the active compounds are made synthetically, however.

Willows and aspirin
• Even in the time of Dioscorides it was known that extracts of willow bark ( Salix spp.,
Salicaceae) and leaves alleviated pain.
• The compound that is responsible is called
"salicin". Salicin is too irritating to take internally, however.
• In the late 1800's, a German chemist made another compound that could be taken readily and that had similar properties to salicin.

Willow in flower, Salix nigra , Salicaceae

• This compound, acetylsalicylic acid, could be taken orally and was an effective analgesic, anti-inflamatory, and antipyretic drug and is probably the most widely used drug in the world today.
• Interestingly, we only learned how aspirin actually functions in the last 30 years. Aspirin inhibits the synthesis of certain prostaglandins.

Coca and cocaine
• The Indians of Andean South America have long used coca leaves (from Erythroxylum coca , Erythroxylaceae) as a stimulant. The
Indians chewed the leaves mixed with lime to free the alkaloids. The alkaloids reduced feelings of hunger and pain.
• Later when the alkaloids were isolated, it was discovered that they had local anesthetic properties. Cocaine has been used for surgery (especially dental surgery).

Coca, Erythroxylum coca , Erythroxylaceae

Steroids from plants
• Many types of animal hormones are steroids.
Although the steroids from plants are similar, most do not have pronounced hormonal activity in animals and ordinarily must be chemically modified before use.
• The most commonly used plant source of steroids is Dioscorea spp. (Dioscoreaceae).
These are viny plants with large tuberous roots.
• Diagram p. 277.

• These steroids occur as complex glycosides
(that is, they have sugars attached) that give them soap-like properties and are sometimes called saponins. These compounds are relatively common in plants.
• Dioscorea species are used because they have relatively large amounts of saponins and the structure of the aglycone is particularly appropriate for conversion to the desired steroids.

Male and female
Dioscorea plants

Disocorea root

• Steroids from these plants are converted chemically into hormonally active substances that simulate pregnancy and serve as antifertility or contraceptive compounds or as anti-inflamatory drugs such as cortisone etc. that are used to treat a number of diseases such as arthritis etc.

Cardiac glycosides
• The use of plants to treat heart disease goes back thousands of years and is found in several cultures. One of the plants found in the folk medicine of Europe is Digitalis purpurea (Scrophulariaceae).

Digitalis, Digitalis purpurea
(Scrophulariaceae)

• In 1775, William Withering, a British physician documented that patients treated with foxglove improved. He standardized the dosage of the drug.
• Diagram p. 277.
• Digitalis became accepted and today is widely used in treatment of dropsy, a condition associated with congestive heart failure.
• The active compounds are saponins, but have an aglycone with a special type of structure.

Opium poppy, Papaver somniferum
(Papaveraceae)
• The alkaloids found in opium poppy, Papaver somniferum (Papaveraceae), have long been used to alleviate pain. See diagram of the plant on page 279.
• Capsules have been found in prehistoric deposits from the Mediterranean and from the
Near East. Pictorial representations are found in Egyptian, Greek, Roman and other art.
• Opium was used to treat dysentery from at least the first century B.C. The wild ancestor of the plant is no longer known with certainty.

Poppy flower and capsule
Carolina Biological Supply Co.

• Opium is isolated by lightly slashing the immature fruit capsules. The latex oozes out and hardens after a day or so. The latex is about 11% morphine and 1% codeine. The exudate is scraped off and made into bricks of pure opium. The yields are 25-40 lbs. per acre.
• Morphine is one of the principal alkaloids of opium. These alkaloids are very addictive, but are potent pain killers (analgesics).
• Codeine, another morphine alkaloid, is a potent antitussive agent, that is, it inhibits coughing.

Incised poppy capsule and latex
Carolina Biological Supply Co.

• Morphine is acetylated to produce heroin.
• Poppies are also cultivated for the seeds which are eaten and are used as an oilseed crop in some countries.
• Opium played a role in the history of China and (especially) British colonialism in the last two or three centuries.

Tropane alkaloids
• A number of alkaloids from solanaceous plants are used as analgesics.
• See p. 280.
• The most commonly used alkaloids are scopolamine (hyosine), hyoscyamine, and atropine.
• The most commonly used plants are Atropa belladonna , Hyoscyamus niger , and Duboisia species (the last species native to Australia).

Henbane, Hyoscyamus niger , Solanaceae

Jimson weed, Datura stramonium , Solanaceae

• Belladonna has been used since the times of the Greeks. It was also used in the Middle
Ages in Europe to enhance the appearance of women by causing them to have large pupils.
• Today, these alkaloids are used as antidotes for poisoning, to treat cardiac problems, for antidiarrhetic preparations, and to dilate pupils during eye examinations.

Black nightshade,
Atropa belladonna ,
Solanaceae

Rauvolfia Alkaloids
• A number of plants of this group were used medicinally in India several centuries BC.
• One of these plants is Rauvolfia serpentina
(Apocynaceae). This plant contains alkaloids that are extremely potent hypotensive agents.
• One of the main alkaloids, reserpine, is used to treat hypertension and certain types of mental illness. Relatively large doses are used to treat schizophrenic patients.

Rauvolfia serpentina
(Apocynaceae)

Catharanthus alkaloids
• Two complex alkaloids of Catharanthus roseus (Apocynaceae) are used to treat leukemia. Vinblastine and vincristine produce remissions or cures in up to 50-70% of cases in certain forms of leukemia. In lymphocytic leukemia, even higher cures are reported.

Periwinkle, Catharanthus roseus (Apocynaceae)

Colchicine
• Colchicine, an alkaloid from Colchicum autumnale (Liliaceae), is used to treat gout. The compound is fairly specific for the disease, but is highly toxic and its use must be carefully monitored.

Autumn crocus, Colchicum autumnale (Liliaceae)
R. Bentley and H. Trimen, Medicinal Plants , London,
Churchill, 1880.

Anthraquinone glycosides
• Anthraquinone glycosides from a number of plants [including Aloe
(Liliaceae), Rhamnus (Rhamnaceae),
Cassia (Fabaceae or Leguminosae)] are widely used as laxatives. They also have other medicinal applications.

Aloe, Aloe sp., Liliaceae

Taxol
• The antitumor activity of taxol (paclitaxel), a diterpene alkaloid from several Taxus species, was first discovered in the 1960's, but the alkaloid didn't become widely used until the mid 1980's.
• Taxol is useful for treating several types of tumors, but was originally developed for ovarian tumors.

• The alkaloid occurs in highest concentration and in the most readily purifiable form in the bark of Taxus brevifolia , the Pacific yew.
• Recently, materials from other species of
Taxus have proven useful for sources of the drug, largely alleviating the environmental problems that resulted from over harvest of the original source.

Yew, Taxus baccata ,
Taxaceae

Calabar bean,
Physostigma venenosum (Fabaceae or
Leguminosae)
• Calabar beans have been used as a trial-by-ordeal plant. The active ingredient, physostigmine, is presently used to treat glaucoma.

Calabar bean,
Physostigma
venenosum (Fabaceae or Leguminosae)
R. Bentley and H. Trimen, Medicinal Plants ,
London, Churchill, 1880

Ergot, Claviceps spp., Clavicepitaceae
• The alkaloids from Claviceps spp. on cereal grains have long caused problems in human health. The compounds are vasocontrictive and in the Middle Ages in Europe caused many human poisoning problems.

Ergot, Claviceps spp., Clavicepitaceae

• People's hands and feet sometimes developed gangrene when they ate grain containing ergot.
• Some of the alkaloids also cause hallucinogenic effects and bizarre behavior.
• All together the syndrome was called "St.
Anthony's fire". The basis for the syndrome was not understood until about 150 years ago.
• Today the alkaloids are used to treat migraine headaches, control hemorrhaging after childbirth, and to induce labor.

• Today, in Western Culture, most of the active ingredients are isolated, purified, and standardized, or ... ironically (in the U.S.) are sold in "Health Food" stores with little assurance that the plant materials are pure, contain the active principles, or are effective.
Recent changes in FDA regulations promise to improve this situation.

• In Europe, particularly in Germany, companies that market herbal medications are required to establish efficacy and to provide the materials in a form that ensures that the active materials are present in a designated dosage. However, in many cultures, the crude plant drugs are still used directly.

Herbal medicines in a Mexican market

St. John's wort, Hypericum perforatum,
Clusiaceae
• St. John's wort, Hypericum perforatum , is effective as an antidepressant drug.
• This plant is native to Europe and Asia, but has been introduced into North America, where it is a common weed.

St. John’s wort, Hypericum perforatum , Clusiaceae

Ginkgo, Ginkgo biloba , Ginkgoaceae
• Extracts from the leaves of Ginkgo biloba , a gymnospermous tree from
China, improve capillary blood flow and improve memory and some aspects of brain function. The active components are diterpenes.

Ginkgo, Ginkgo biloba ,
Ginkgoaceae

Ginseng, Panax ginseng , Araliaceae
Ginseng has long been used by Oriental peoples as a way of maintaining health and for treating and curing many types of human ailments. In Japan, Korea, and China, the most common species is Panax ginseng .
Because of the shape of the roots, based on the doctrine of signatures, this plant was presumed to treat many problems.
The Eastern North American species, Panax quinquefolia , was one of the earliest exports from the
American Colonies to the Orient. The active compounds are triterpenoid glycosides; some are called gensenosides.

Ginseng, Panax ginseng ,
Araliaceae
Takatori. Color Atlas of Medicinal Plants of
Japan.

Echinacea , Echinacea purpurea , Asteraceae
Echinacea was used as a medicinal plant by American
Indians. The plant was introduced into patent medicines in the 1870s and has been used since that time to deal with a number of problems.
Echinacea was an important plant medicine in the 1920s, but fell into disuse as antibiotics of various types were introduced.
Echinacea induces an immune response in humans and has been used more recently to treat colds and other viral diseases.
This plant drug is especially popular in Europe. As the plant is often wild harvested, there are many conservations concerns about the continued unrestricted use of this valuable resource.

Echinacea , Echinacea purpurea , Asteraceae

Valerian, Valeriana officinalis , Valerianaceae
Valerian has long been used as a sedative. The dried roots and rhizomes have been used as a tranquilizer and calmative for more than 1000 years in cases of nervousness and hysteria. The plant parts have a somewhat disagreeable odor.
Interestingly, in this case, the active components have never been conclusively identified. However, the plant is documented to be an effective sleep-inducing drug.

Valerian, Valeriana officinalis ,
Valerianaceae

Black cohosh , Cimicifuga racemosa ,
Ranunculaceae
• The underground parts of Cimicifuga racemosa are used to treat a number of
“female problems”.
• This plant was used by many of the American
Indians of the Eastern United States.

Black cohosh , Cimicifuga racemosa ,
Ranunculaceae
• An infusion of the roots and rhizomes is drunk to treat rheumatism, uterine difficulties to stimulate menstrual flow, and as an antidiarrheal, and cough suppressant.
• It was the active component of Lydia
Pinkham’s Vegetable Compound in the 1800s and early 1900s.
• The plant has been shown to have estrogenic activity and is used in Europe to treat premenstrual syndrome (PMS).

Black cohosh , Cimicifuga racemosa , Ranunculaceae