Transcript Medicinal Plants

Medicinal Plants
David S. Seigler
Department of Plant Biology
University of Illinois
Urbana, Illinois 61801 USA
[email protected]
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 (384322 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
Drying and storing
cinchona bark
Courtesy Dr. Walter Hodge
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.
Herbal medicines
• 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