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Medicinal Plants


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Title: Medicinal Plants

Medicinal Plants
  • Medicine in pre-scientific times
  • Synthetic organic chemistry and medicine
  • Alkaloids
  • glycosides
  • Foxglove (digoxin)
  • Willow bark (aspirin)
  • quinine
  • Ephidrine
  • Schizophrenia and resperine
  • cancer treatment
  • Chapter 19

Plants in Medicine
  • The idea of using plants for healing goes back to
    very ancient prehistoric times in all cultures.
  • Neanderthal burial with useful medical plants
    from 60,000 years ago. Shanidar Cave in Iraq.
    Buried with 8 plant species, 7 of which have
    medicinal uses. (I note that skepticism is
    needed here some researchers now think these
    plants (clumps of pollen, actually) were buried
    there by rodents long after the person died.)
  • Otzi the Iceman, who died about 5200 years ago
    and was preserved in a glacier in northern Italy,
    carried two lumps of birch fungus, which can be
    used as both a laxative and an antibiotic. He
    had intestinal parasites.
  • Some animals also seem to use plants as medicine
  • Basic problem with archeological evidence plant
    material decays easily, especially if it is

Medicine in Early Civilizations
  • Sumerian clay tablets with cures
  • Egypt Ebers papyrus (3500 years ago)
  • Shen-nung, the Chinese emperor who also invented
    agriculture, wrote a book about medicinal herbs,
    which he tested on himself.
  • Rig-veda in India
  • Badianus manuscript is an illustrated guide to
    pre-Columbian Aztec herbal medicine. Translated
    into Spanish from native language by Badianus,
    but written by an Aztec healer of high repute.
  • Hippocrates (400 BC) ancient Greek healer.
    Medical doctors take the Hippocratic Oath.
    Western medicine was founded on his works.
  • Dioscorides (100 AD) was a Roman who compiled De
    Materia Medica, which discusses 600 plants of
    medicinal value.
  • Galen
  • Avicenna (1050 AD) was a Persian whose Canon of
    Medicine built on Dioscoridess work.

  • The Renaissance in Europe was a revival of
    ancient learning and intellectual activity, a
    turning away from uncritical acceptance of the
    Bible as the source of all knowledge. Roughly
    1300-1650, starting in Italy and varying by
    region. The period between medieval times and
    modern times.
  • Invention of the moveable type printing press in
    1450 allowed wide dissemination of knowledge.
  • A word for you (that wont be on the test)
    incunabula a book published before 1500.
  • Many herbals, illustrated books describing plants
    and their uses, were published. Practical uses
    together with a lot of mysticism, superstition,
    and what we now consider pseudoscience astrology
    for example.
  • Doctors and other healers had gardens where they
    grew useful plants. Others were harvested from
    the wild.

Doctrine of Signatures
  • The Doctrine of Signatures (which is known to be
    false!) was popular in these books herbs that
    resemble parts of the body can be used to heal
    those parts.
  • Liverwort, lungwort, bloodroot, snakeroot
    (healing snakebite), for example.
  • Advocated by Paracelsus (1500 AD). But, the idea
    is found in many cultures.
  • The idea Since God created the world for us
    humans, He marked things with a sign (a
    signature) indicating their use.
  • Also linked to this the idea that the cure for
    every disease can be found near where the disease
    is common.
  • The history of science is filled with
    counter-examples. We have to figure out the uses
    of plants and other objects by experiment and
    observation. How a plant looks is not related to
    how it will interact with the human body.
  • That is, sometimes there is a correlation between
    how a plant looks and how it is used, but it
    isnt a causal relationship. That is, you might
    find a plant useful for some purpose and then
    find an aspect of its appearance that helps you
    remember that use, but if you see a plant that
    you think resembles some part of the body, it
    probably wont specifically affect that body
  • You can think of the Doctrine of Signatures as a
    useful mnemonic device, but it isnt a guide to
    how novel plants will work.

Some Examples
Hepatica leaves have 3 lobes, just like the liver
Walnut looks sort of like a brain!
Tomatoes are red and have four chambers, just
like the heart.
Pre-Scientific Medicine
  • Across all cultures, healing the body was very
    mixed up with religious belief. In the absence
    of an effective cure, prayer seemed like the only
  • It wasnt clear what worked and what didnt.
    Medicine was based on anecdotal evidence I as a
    doctor tried such-and-such a cure, and it worked
    or it didnt, and I change my opinions about what
    to use in a given situation based on this.
  • Also, written works passed down from the ancients
    (such as Hippocrates) were given great weight.
  • This led to medicinal recipes with many
    ingredients, most of which had no effect.
  • And some of which were there just to produce
    drama many patients felt that an effective cure
    had to make them vomit or otherwise go through an
    unpleasant physical experience to start the
    healing process.
  • Many people get better from good nursing keeping
    them warm and well fed and rested, and paying
    attention to their complaints. The body has
    great power to heal itself if given a chance.
  • This led to medicines being given credit for
    cures they didnt deserve.

Systems of Medicine
  • Our present system, scientific medicine, is only
    200 years old or so. There have been many other
    concepts in medicine, and there continue to be
    alternative systems of medicine. These other
    systems often contain concepts that are
    specifically denied or disproved by science.
  • Hippocrates and the Four Humors blood, phlegm,
    black bile, and yellow bile. The humors have
    properties of hot, cold, wet and dry. In disease,
    the humors get out of balance. The theory formed
    the basis of Western medicine until the 1850s or
  • We get words for personality traits like
    sanguine, phlegmatic, choleric, and bilious from
    this theory.
  • This theory also encompasses the idea of the four
    elements earth, air, fire, and water.
  • Traditional Chinese medicine and Ayurveda
    (traditional Indian medicine) are also
    alternative theories of medicine that remain
  • Francis Bacon, an early scientific philosopher,
    said. This is the foundation of all. We are not
    to imagine or suppose, but to discover, what
    nature does or may be made to do.

Scientific Testing
  • The essence of the scientific method is the
    controlled experiment the subjects are divided
    into two groups, with one group given the
    experimental treatment and the other given a
    control treatment.
  • The control treatment should be as similar to the
    experimental as possible, just missing the one
    element being tested.
  • A useful refinement double-blind experiments,
    where neither the patients nor the doctor knows
    who is getting the experimental treatment and who
    is getting the control. This avoids the placebo
    effect, where patients often get better even with
    a control treatment.
  • Statistical analysis of the results is necessary,
    because random factors influence the results. An
    important feature of statistics using enough
    subjects to get statistically significant
  • Animal models for the disease are very useful
    you can do more experiments without upsetting
    patients and their families.
  • More recently, tissue culture cells and even
    simpler model systems can sometimes be used.

Statistical Analysis
  • Allows decision making based on math and not just
  • A major fallacy that statistics is designed to
    reduce is basing conclusions on anecdotal
    evidence (one or a small number of observations
    that occurred to someone you know). Your
    brother-in-laws cousin won the lottery while
    wearing a rabbits foot, so you now go out and
    get a rabbits foot too.
  • common things to calculate from the data mean
    (the average) and standard deviation.
  • Many results fall into a bell-shaped curve.
    Standard deviation is the width of the curve the
    points on the curve where 2/3 of all
    observations fall between. For example a group
    of men has average (mean) height of 176 cm plus
    or minus 10 cm (176 ? 10) means 2/3 of everyone
    was between 166 and 186 cm.
  • Conclusions based on statistics take both the
    mean and the standard deviation into account how
    much do the two groups overlap?

Active Principles
  • A big idea from the early 1800s The reason that
    certain plants are effective against particular
    diseases is because they contain specific
    chemical compounds (the active principles) , with
    the rest of the plant material irrelevant.
  • If you isolate (or synthesize) the active
    principle, you can control the dosage people are
    given and avoid giving them other plant compounds
    that might have bad side effects.
  • In contrast, the amount a plant contains can vary
    with environmental conditions, age of the plant,
    the plants genetics, and many other factors.
  • Also, it is possible to determine whether a given
    plant is actually effective, or which parts of
    mixtures are important.
  • This concept led to people trying to extract the
    active principles from plants. For instance
    which works better, soaking the plant material in
    cold water, hot water, alcohol, etc.? Which part
    of the plant produces the most active principle?
  • Lots of help from alchemy, the precursor to
    modern chemistry.

Organic Chemistry
  • It was once thought that "organic" chemical
    compounds could only be made by living organism
    that's what "organic" means.
  • The doctrine of Vitalism, which is now thought to
    be false living organisms and their components
    are endowed with a "vital force" that is separate
    from their chemical reactions.
  • Nowadays we think of life as just a set of
    complex chemical reactions. I wish to note,
    however, that so far no one has been able to
    create life in the laboratory.
  • In 1828, Friedrich Wöhler synthesized urea (waste
    product from nitrogen in protein) from inorganic
    compounds. Followed by many others. Vitalism
    loses vitality "The great tragedy of science,
    the slaying of a beautiful hypothesis by an ugly
    fact.", to quote Wöhler.
  • We now believe that any chemical compound found
    in living organisms can be synthesized in the
    laboratory from simple precursors.
  • We don't necessarily know how to create some of
    the more complicated one, but it isn't considered
  • Organic compounds now just mean those containing
    carbon. A few exceptions like carbon dioxide are
    mostly for historical reasons.

More Organic Chemistry
  • Another big event mauve dye synthesized
    accidentally, while trying to make quinine. It's
    a big seller suddenly there's money to be made
    in organic chemistry.
  • In 1863, Friedrich Kekule describes how carbon
    bonds with other atoms the structure of organic
    compounds becomes clear.
  • His breakthrough idea, how the 6 carbons in
    benzene link into a ring, came to him in a dream.
  • Synthesis in multiple step processes, separation
    techniques, analytical methods, lots of chance
  • Germany was the leader in this field.
  • How this relates to medicinal plants You can
    modify the structure of useful chemical compounds
    and sometimes make them more effective, or have
    fewer side effects, or more stable during
    storage, or other useful properties.

Medicinal Chemistry
  • The effect of organic chemistry and the
    scientific method useful compounds are still
    isolated from plants taxol is a recent example.
    However, once isolated, attempts are made to
    synthesize them and modify them.
  • This helps avoid the supply of the plant from
    being cut off due to disease or political or
    economic reasons.
  • The Germans pioneered this philosophy of
    self-sufficiency in the 1800s because they had
    poor access to the ocean trade routes and very
    few overseas colonies.
  • Also, synthesizing an active principle from
    scratch proves that you really do understand its
  • It is worth considering whether the healing
    effect of a plant is due solely to a single
    active compound, with all others irrelevant.
    There are many cases where several compounds
    acted synergistically. And, healing is also
    helped by the placebo effect and also by careful
    individual attention from a healer. We are not
    just biological machines that respond uniformly
    to impersonal treatment.

Drug Discovery
  • Where do new medicinal drugs come from?
  • More precisely where do drug families come from,
    since once a useful pharmaceutical drug has been
    discovered, it gets modified in thousands of ways
    by chemists trying to improve it.
  • In the past, two sources compounds suggested by
    traditional herbal medicine, and serendipitous
    (random chance) discoveries.
  • Today, rational drug design is becoming
    important understanding of how the disease works
    and where it might be intervened with, coupled
    with knowledge of the physical structure of
    enzymes involved allows the design of completely
    new drug molecules.
  • Also, combinatorial chemistry start with a
    useful compound, make a large library of modified
    versions, then test them all against a target.
  • The whole process of discovering and testing a
    new drug is very expensive and laborious let's
    say 1 billion and 10 years to get from
    discovering a new drug to getting it on the

Active Principles in Plants
  • The value of plants as medicine come from
    specific chemical compounds they contain. These
    compounds are secondary metabolites not directly
    related to the plants ability to grow or
  • Secondary metabolites are probably present as a
    defense against infection by bacteria or fungi,
    or to prevent insects and other animals from
    eating them.
  • Some secondary metabolites inhibit other plant
    species they poison the soil.
  • Also, some are used to attract animals to help
    with pollination and seed dispersal the scents
    of fruits and flowers, for example.
  • Different species produce different secondary
    metabolites. Within plant families, the secondary
    metabolites are similar. For instance, the
    carrot family and mustard family.
  • A 2001 study counted 122 compounds used in
    medicine that were derived from traditional
    herbal medicine. Of these, 80 were used for
    the purpose the herbalists said they were good
    for. Traditional herbal medicine is a very
    useful starting point for drug discovery.
  • It is thought that about 10,000 different plants
    have been used in herbal medicine at some point
    in human history.

Major Groups of Secondary Metabolites
  • Alkaloids. Many different compounds, found in
    many plants. They all contain nitrogen atoms,
    are alkaline (basic), and taste bitter.
    Structures vary widely.
  • Often affect the nervous system. Whether this is
    good or bad depends on dosage and your point of
    view. For example, morphine.
  • Glycosides. A sugar is attached to the active
    component. This makes them non-toxic until an
    enzyme removes the sugar, which happens in the
    digestive system.
  • Cyanogenic. Very simple cyanide attached to a
    sugar. Remove the sugar and release the poison
    it stops the ability to make ATP.
  • Steroid. Steroids have a particular ring
    structure and are used to make hormones in
    animals. Two main types
  • cardioactive (meaning that they affect your
  • Saponins are soapy and very toxic they work
    especially well as fish poisons because they
    dissolve easily in water. The steroid found in
    yams (Dioscorea) is a saponin.

  • ss

Some Glycosides
  • Malaria is a disease native to Africa. It has
    probably evolved with us for a very long time
    closely related diseases affect chimpanzees,
    gorillas, and other mammals.
  • Malaria is thought to killed more people than any
    other infectious disease. It kills between 1 and
    3 million people a year, mostly young children in
    sub-Saharan Africa.
  • It is widespread in the tropics throughout the
    world, and it can be found in temperate areas as
  • Many Southern cities used to empty out in the
    summer as anyone with sufficient resources would
    leave town to avoid malaria, going to hill
    country or the seashore.
  • Large effects on war. More soldiers died of
    disease (often malaria) than by violence until
    modern times. Nomads had less malaria than city
    dwellers, which gave them a big advantage.
  • After malaria came to the New World, Native
    Americans had no resistance and many died of it.
    In contrast, Africans often had resistance, so
    they worked better as slaves.

Malaria Cases in 1996
Malaria as a Disease
  • The disease is caused by a single celled
    eukaryotic parasite called Plasmodium falciparum,
    plus a few closely related species of Plasmodium.
    The parasites are highly adapted to humans and
    have several ways of evading the immune system
    and remaining dormant.
  • The disease itself is cyclical first you get
    chills, then a fever, then fever with sweats
    (cold-dry, hot-dry, hot-wet). Then, a feeling of
    complete exhaustion. At this point you either
    die or fall asleep for a while and wake up
    refreshed. Then the cycle starts again, with a
    2-3 day period.
  • The parasites live in red blood cells, and when
    they rupture the cells, the victim gets anemia
    and a heavy dose of toxic hemoglobin derivatives.
  • Malaria can be a chronic recurring disease many
    people never get rid of it, and it can start up
    again at any time.
  • Other symptoms include severe headaches caused by
    intracranial pressure, renal failure (blackwater
    fever), anemia, enlarged spleen and enlarged

Malaria and Mosquitoes
  • Malaria has long been associated with swamps. The
    word malaria means bad air is Italian it was
    thought that the disease was caused by the
    poisonous vapors of the stagnant water and
    rotting vegetation. This theory goes back to
  • Called ague in other places mentioned several
    places in Shakespeare.
  • In the 1850s it was recognized that malaria was
    caused by a parasite spread by mosquitoes.
  • An amusing wrong turn in 1878, a bacterium was
    alleged to be the cause of malaria (the Germ
    Theory of Disease as the answer to all problems).
    The problem with this bacteria are much easier
    to kill than eukaryotic parasites because as
    prokaryotes, the metabolism of bacteria differ in
    major ways from that of eukaryotes.
  • The actual life cycle of the parasite was worked
    out n the late 1800s and early 1900s.

Malaria Life Cycle
  • The Plasmodium parasite needs to be in three
    different locations to complete its life cycle.
    It undergoes several changes of form during the
  • Human liver. Shortly after the mosquito injects
    the parasites, they migrate to the liver. Some
    of the parasites can remain dormant in liver
    cells for months or years, periodically releasing
    the next stage of parasites into the blood and
    causing a relapse of disease symptoms.
  • Human red blood cells. After multiplying and
    changing their form in the liver, the parasites
    move into the red blood cells. They multiply and
    burst the blood cells, causing the disease
  • Mosquitos gut. After a mosquito ingests
    infected blood, the parasites undergo sexual
    reproduction in its gut, and the resulting
    parasites migrate to the salivary gland.
  • The cycle repeats when the mosquito bites a new

Malaria Prevention
  • The most effective way to eliminate malaria has
    been to eliminate the mosquitoes that carry the
  • Eliminating swamps and stagnant water has
    historically been the most effective method.
  • The insecticide DDT was used very effectively
    from the 1940s to the 1970s. Unfortunately it
    is quite persistent in the environment and toxic
    to birds and other animals. Its used was banned
    for most purposes.
  • Similarly, spraying stagnant water with kerosene
    was effective for control, but it kills the fish.
  • Sleeping under insecticide-treated mosquito nets
    can be quite effective.
  • Very little malaria in the US or Europe any more
    due to effective mosquito control measures.

Genetic Resistance to Malaria
  • Natural selection for malaria resistance has
    caused the spread of several human genetic
    conditions that affect red blood cells.
  • These conditions are otherwise very harmful.
  • Sickle cell anemia is an alteration of hemoglobin
    that causes it to crystallize into long rods when
    oxygen gets low (while exercising, for example).
    This causes the blood cells to get distorted and
    kills the parasites. The mutation seems to have
    arisen at least 4 times independently in
    different parts of Africa, and once in India.
  • Other hemoglobin diseases, called thallassemias,
    also protect against malaria. There are many
    forms, found in the Mediterranean region all the
    way across Asia to Indonesia.
  • Several other diseases affecting the red blood
    cells also confer some malaria resistance and are
    found in the malaria belt.

  • Quinine is an alkaloid found in the bark of the
    cinchona tree, which grows in the Andes
    Mountains, mostly in Peru. It was used to reduce
    fever by the native peoples. 1630s.
  • The tree was named after the Countess of Chinchon
    by Linnaeus (who accidentally left out an h).
    She was the first known European user of the bark
    as a malaria treatment.. All other treatments
    had failed, so her physician decided to try a
    medicine obtained from local healers. (This
    story may be less than historically accurate).
  • Quinine kills the malaria parasites in the blood.
    Since the parasites also live in the liver,
    quinine must be taken daily to prevent a relapse
    of the disease.
  • The supply was controlled by Jesuit priests for a
    long time, and so the medicine was known as
    Jesuits bark.
  • It worked very well in many cases, unlike all
    other malaria cures.
  • However, some bark worked better than others, due
    to concentration differences n quinine. High
    altitude trees produced much more than sea level
  • Oliver Cromwell, an English revolutionary in the
    1600s, died of malaria rather than use a product
    associated with the Roman Catholics he hated.

More Quinine
  • Gathering the bark kills the trees, so demand
    started to far outstrip supply. Quite expensive,
    and headed for extinction.
  • In 1860, the British started growing cinchona in
    India and Sri Lanka (after stealing the seeds).
    Spread to Dutch Indonesia also.
  • Quinine is quite bitter, which led to the
    development of the mixed drink the gin-and-tonic.
    This drink was developed by the British army in
    India during the 1700s. It is used to flavor
    and dilute the alcohol in gin, and make its
    administration much more pleasant. Tonic water
    was originally a mixture of quinine and
    carbonated water, with sweeteners added to ease
    the bitterness. The juniper berry taste of gin
    complements the bitterness of the quinine.
  • Cheap and plentiful quinine from India allowed
    Indians, Chinese, and Europeans to live many
    places they hadnt beforehand.

Distribution of the 20 million Indians living
outside India
New World Quinine vs. Old World Malaria
  • The oddity here the cure for a disease was in a
    plant that didnt grow anywhere near where the
    disease was. Is this just a chance event? What
    is the natural selection (scientific) reason why
    quinine existed in that bark? Just a general
    plant defense mechanism it tastes bad? Is it
    just chance that it happened to fit a human
    problem very neatly? What did the American
    native people use it for, and why does it work
    for that, or why did they think it did?
  • What about the possibility that malaria existed
    in the New World before Columbus? Evidence
    against it no natural genetic resistance, with
    lots of it in the Old World. Also, Aztec and
    Mayan records dont describe the disease in a way
    that anyone has been able to recognize.
  • Used it for fever and a muscle relaxant
  • The old doctrine that every disease has its cure
    somewhere in the vicinity. Probably comes from
    some ancient healer like Hippocrates or Galen.
    But, there is no reason to think its true. It
    describes a Universe that is set up for our
    purposes. In the world of Science, we dont
    consider that a valid concept.
  • There are undoubtedly many medically useful
    compounds in plants that have not been discovered
    yet a good reason to maintain biodiversity.

  • Many anti-malarial drugs have been developed.
    Artemisinin is the active principle in the plant
    Artemisia annua (wormwood). This plant has been
    used in traditional Chinese medicine to treat
  • In the 1960s, Chinese scientists tested 200
    traditional medicines that had been used to treat
    malaria. Only this one worked.
  • It also works against other blood parasites such
    as schistosomes (blood flukes).
  • The drug has been modified by organic chemists to
    make it more stable and usable by the human
    metabolic system.
  • Current work on malaria includes much effort to
    develop a vaccine. Unfortunately, the parasite
    is very good at evading the immune system.

  • Today, aspirin is probably the most widely used
    synthetic drug. However, it originated in the
    plant world.
  • The inner bark of willow trees, made into a tea,
    has been used for relief of pain, fever, and
    inflammation since ancient times. Hippocrates
    discussed in ancient Greece, and it is also
    mentioned in medical works from ancient Sumerian
    city of Ur in 3000 BC. Native American tribes
    also used it.
  • The active ingredient in willow bark is salicylic
    acid. It is a plant hormone it is released when
    the plant is wounded, and stimulates the cells to
    strengthen their cell walls and produce enzymes
    and other compounds to fight the infection.
  • It also gets converted to a volatile form, methyl
    salicylate (which is Oil of Wintergreen). This
    compound induces pathogen defense mechanisms in
    nearby plants.
  • Salicylic acid was extracted from willow bark in
    the early 1800s.

More Aspirin
  • Salicylic acid is very irritating. It gets used
    today as a wart remover! In low concentrations,
    it is used to exfoliate the skin (remove dead
    cells) and unclog pores. It also was very hard
    on the stomach, which limited its usefulness.
    However, salicylic acid was used as a painkiller
    in the middle 1800s.
  • In the 1890s, chemists at Bayer Laboratories in
    Germany developed a derivative, acetyl salicylic
    acid, that was less harsh.
  • It was marketed as aspirin.
  • During World War 1, the Bayer patent on aspirin
    was voided in Britain, and aspirin became a
    term anyone could legally use.
  • After the US entered World War 1, all of Bayers
    property was auctioned off, including even the
    name Bayer Aspirin. The Bayer company survived
    in Germany, and in 1994, they bought back the US
    rights to their own name for 1 billion.

How Aspirin Works
  • Aspirin reduces the production of prostaglandins,
    by inhibiting the enzyme cyclooxygenase (COX).
    COX converts the fatty acid arachidonic acid into
  • Prostaglandins are molecules that act as local
    hormones, transmitting signals between cells.
    They are released from injured cells. They
    sensitize pain nerves so fire more easily,
    meaning that you feel more pain.
  • They also raise the bodys internal temperature.
  • Aspirin also inhibits blood clotting. It is
    often used in low doses to prevent heart attacks.

COX-2 Inhibitors
  • There are 2 forms of COX. Aspirin inhibits both
    of them. But newer drugs inhibit just COX-2.
  • COX-1 produces prostaglandins in the digestive
    system that protect it, while COX-2 produces
    prostaglandins responsible for pain and
    inflammation. Aspirins well known properties as
    a stomach irritant are due to its inhibiting
    COX-1 in addition to COX-2.
  • Drugs inhibiting COX-2 only have been found.
    Vioxx and Celebrex became very popular drugs for
    treating arthritis and chronic pain. They are
    much easier on the stomach than aspirin is.
    However, they seem to cause an increase in blood
    clots and heart attacks. In light of this, Vioxx
    was taken off the market and use of Celebrex is
    greatly decreased.

Foxglove and Dropsy
  • Foxglove (Digitalis purpurea) is an Old World
    plant, found in much of Europe, western Asia and
    northern Africa. It is a biennial. In the first
    year it makes a rosette of leaves close to the
    ground, and in the second year is grows a tall
    flower stalk. It is a common ornamental garden
    flower. All parts of it are quite poisonous!
  • Long a part of many herbal cures
  • Congestive heart failure (called dropsy in the
    old days) is a condition where the heart cant
    pump enough blood to satisfy the bodys needs.
    It is a slowly progressing condition, not a
    sudden stopping of the heart.
  • Symptoms swelling of feet, ankles, and lungs due
    to fluid buildup, shortness of breath, general
  • Retention of fluid is called edema.
  • Problem is, the heart cant push the blood
    through the kidneys with enough force to get them
    to work properly in excreting all the water.

Digitalis as Herbal Medicine
  • William Withering was an English doctor in the
    1700s. He also wrote a book about English
  • Withering hated botany in college, but he fell in
    love with a woman who liked to paint flowers, and
    while collecting them for her he became devoted
    to botany.
  • He had a patient with very bad dropsy, who he
    expected to die within days. A few weeks later
    he returned, and she was alive and much
    healthier. He learned that she had used an
    herbal recipe kept secret by an old woman in
    Shropshire . It was very effective in relieving
    the symptoms of dropsy.
  • There were 20 or more components to the recipe,
    but, after paying the herbalist a good sum of
    money, learned that foxglove was the important
  • Other ingredients were present to induce vomiting
    and other side effects, which proved to the
    patient how strong the medicine was.
  • He spent 10 years researching which part of the
    plant was most effective, when to harvest it, how
    to extract it, and what the optimum dose was.
  • Previous dropsy treatment puncture the tissues
    with a (non-sterile) scalpel, then stretch the
    patient over bedsprings and collect the fluid in
  • Some doctors didnt approve of foxglove as a
    treatment, since it had its origins in
    witchcraft. Also, many cases of overdose
    occurred (if a little bit is good, then a lot
    must be better!). Also, it didnt cure other
    diseases that herbalists alleged it was good for

  • The active chemical compounds in foxglove were
    isolated in the early 1900s. They are several
    steroid glycosides, with the most active one
    being digoxin. It is still used in treating
    congestive heart failure.
  • Digoxin increases the pumping force of the heart
    muscles. Too much can lead to a heart attack.
  • Heart disease is the leading cause of death in
    the US. Dropsy was very common 200 years ago,
    but it is easily treated today.

Coumarin and Blood Clotting
  • Coumarin is a chemical compound that produces the
    smell of freshly mown grass. It is used in the
    perfume industry, as a substitute for vanilla,
    and as a flavoring agent for tobacco.
  • Coumarin can be converted into a powerful
    anti-coagulant by enzymes found in fungi.
  • The blood doesnt clot, causing the victim to
    bleed to death.
  • Origin In the 1920s, cows at Wisconsin dairy
    farms started bleeding to death after de-horning
    or castration, and some just spontaneously. A
    little observation showed that it occurred after
    that had eaten hay that had been made from sweet
    clover and was moldy. Non-moldy hay had no
  • Chemists at the University of Wisconsin developed
    an assay for blood clotting using rabbits, and
    after several years of effort, they isolated the
    active compound.

More Coumarin
  • Clover makes good silage cows like the way it
    tastes. Care must be taken to prevent fungal
    infection, which converts the sweet-smelling
    coumarin to the anti-coagulant dicoumarol.
  • It proved to be useful for preventing blood
    clots, which can kill by blocking blood
    circulation in the heart or brain.
  • Once dicoumarol was isolated, various chemical
    modifications were tried, and soon a much
    stronger one, warfarin, was created.
  • Named for the Wisconsin Alumni research
    Foundation (WARF).
  • Warfarin interferes with vitamin K, which is
    needed for blood clotting. The antidote to
    warfarin is large doses of vitamin K.

  • Warfarin is primarily used as rat poison. It is
    odorless and tasteless, so rats will eat it when
    mixed with food. It usually takes several
    feedings to build up a lethal dose, so the rats
    dont associate it with the food.
  • Mice and rats are bad to have around. They eat
    and contaminate our food. They spread salmonella
    and other diseases through their feces, which get
    everywhere in an infested house. They gnaw wires,
    pipes and wooden structures. The fleas on rats
    carried (and in some places still carry) bubonic
  • By now, mice and rats have a lot of resistance to
    warfarin, so its use is declining.
  • There is a theory that Jozef Stalin was killed by
    his successor Nikita Khrushchev using warfarin in
    1953. Stalin was the head of the Communist Party
    in the Soviet Union, which made him the absolute
    ruler of that country,
  • I find this a bit ironic a discrepancy between
    the expected result and actual results when
    enlivened by perverse appropriateness..

  • Ephedrine is a stimulant and nasal decongestant.
    It is chemically similar to amphetamines. It is
    an alkaloid derived from plants in the genus
    Ephedra, which (unlike almost all other plants we
    are examining) is a gymnosperm.
  • It has long been used in traditional Chinese
    medicine to treat asthma and bronchitis.
  • In sports, ephedrine is considered a
    performance-enhancing drug and is banned.
  • A big reason why ephedrine is regulated
    Baltimore Orioles pitcher Steve Bechler died in
    2003 with ephedrine toxicity playing a
    significant role. He died of a heatstroke at
    the beginning of spring training in the hot
    weather of south Florida.
  • The illegal dugs methamphetamine and MDMA
    (Ecstasy) can be made relatively easily from
    ephedrine and its close mimic pseudoephedrine
    (also found in plants). For this reason, most
    states regulate the amount you can buy.
  • In Illinois you are required to show
    identification, give them your address, and you
    can only but 1 package a day.

Reserpine and Schizophrenia
  • Snakeroot is the common name of several unrelated
    plants with long coiled roots. It fits the
    Doctrine of Signatures quite well, and so it has
    been used to treat snakebite in several different
  • We are concerned here with Rauwolfia serpentina,
    the snakeroot that grows in India. It is also
    used in traditional Chinese medicine, and was
    discovered by the semi-legendary emperor Shen
    Nung. It was used as a general poison antidote,
    and as a tranquilizer and cure for insanity.
  • In the 1950s, the alkaloid reserpine was
    isolated from snakeroot. It acts as a sedative,
    and was used as a treatment for schizophrenia.
    It also lowered blood pressure
  • Today, resperine is mostly used to combat high
    blood pressure. It causes the blood vessels to
    relax. However, other drugs have taken its place.
    Hypertension is a major medical issue, so much
    scientific effort goes into finding drugs to
    control it effectively. The sedative effects of
    reserpine are a strongly negative side effect for
    this use.

  • About 1 of the US population has some form of
    schizophrenia. Most develop it between ages 16
    and 30, and only rarely after age 45. It can be
    hard to recognize in younger people.
  • lose touch with reality
  • hallucinations (seeing or hearing things that
    arent there). Voices telling you what to do,
    invisible fingers touching you, smelling odors no
    one else can detect. Hearing voices is the most
    common symptom.
  • Delusions false beliefs that cannot be changed
    by facts (especially if they are not common in
    your culture). People of television are speaking
    directly to you, radio waves are controlling your
    behavior, belief that you are a famous historical
    figure (like Napoleon), belief that others are
    plotting against you or trying to harm you.
  • Movement disorders agitated body movements,
    repeating the same motions over and over, walking
  • flat affect your face shows no emotion and you
    talk in a dull monotone
  • Inability to plan, or sustain planned activities,
    or make decisions.
  • inability to interact with others properly
    speech is disconnected and makes no sense to

What Causes Schizophrenia?
  • The actual cause isnt clear, but both genetics
    and the environment play a role.
  • Genetics it runs in families. The risk in the
    general population is 1, but its 10 if a
    sibling or parent has it, and 50 if an identical
    twin has it. However, no specific gene is known
    to cause schizophrenia, despite serious efforts
    to find one. It is a complex genetic trait
    probably many genes contribute small amounts to
    your risk.
  • Environment possibly virus exposure or
    malnutrition before birth play a role (but no
    specific viruses have been identified). Trauma
    child abuse and neglect seems to play a
    significant role in the development of some
    schizophrenia. Post-traumatic stress disorder
    and other adult traumas may also play a role.
    Hallucinogenic drugs such as LSD can trigger
    schizophrenia in people who are pre-disposed to
    get it.
  • Marijuana use is high among schizophrenics, and
    tobacco use is also far above the general
    population, but this may be the result of
    self-medication and not causation. But, marijuana
    may increase the risk.
  • No obvious differences in brain structure
    associated with schizophrenia. It is strictly a
    mental illness.

  • Old days jail, insane asylum, being treated as a
    witch or possessed by demons. Or, occasionally
    treated as a saint communicating with God.
  • Pyschosurgery. The lobotomy involved destroying
    part of the frontal lobes of the brain. It became
    very popular in the 1940s, but in the 1950s,
    psychoactive drugs were shown to be more
    effective and less damaging.
  • Electroconvulsive therapy. Mostly used for
    chronic depression today.
  • Drug treatment. First generation drugs included
    reserpine and thorazine. Newer drugs target the
    dopamine system in the brain.
  • They have some side effects like drowsiness and
    dizziness. Also, major weight gain and an
    increased risk of diabetes.
  • Long term use can result in tardive dyskinesia,
    which is uncontrollable muscle movements.
  • If you stop taking the medication abruptly,
    relapse can occur. Many people stop taking them
    because they feel better and the side effects get
    intolerable. Drug treatment may need to be
  • Different people respond to different drugs in
    different ways it is necessary to try several
    out to find the best one.
  • Behavioral treatment it is possible to develop
    mental skills to manage the disease to ignore
    the voices in your head, to act normal even if
    you dont feel normal, to rest the reality of
    your thoughts. Self-help groups and family
    education help a lot.

Saints, Demonic Possession, Insane Asylums
  • z

  • The lobotomy (also called leucotomy) was invented
    by Portuguese doctor Egas Moniz, who won a Nobel
    Prize for it in 1949.
  • The idea was to destroy the prefrontal cortex, or
    sever their connection to the rest of the brain.
    It was meant to help cases of severe mental
    illness, at a time when there was no effective
    treatment. Psychotic people were simply confined
    to insane asylums before this.
  • The prefrontal cortex the part of the brain
    immediately behind the eyes, which is involved
    with the executive function of the brain
    predicting outcomes, differentiating between
    conflicting ideas, personality expression,
    decision making and social behavior.
  • Walter Freeman, an American psychiatrist,
    simplified the procedure so it could be done in
    cheaply in a mental hospital. A thin instrument
    was placed under the eyelid and against the top
    of the eye socket. Then it was pounded through
    the thin bone into the brain with a mallet. The
    instrument was swept from side to side, severing
    the connections. Repeated on the other side.
  • Approximately 40,000 lobotomies in the US in the
    1940s and early 1950s. Freeman drove around in
    a lobotomobile, performing the surgery at
    mental hospitals. Stopped with the advent of drug
    therapy. Freeman lost his medical license after
    killing a patient.

Cancer Treatments
  • Cancer is the uncontrolled division of cells that
    eventually overwhelm the normal functions of the
  • Normal cells stop dividing in response to
    signals wound healing, for example.
  • Cancer always starts with a single cell. It
    takes 4 or 5 separate mutations to transform a
    cell to the cancerous state. It multiplies into
    a tumor.
  • In addition to uncontrollable division, a growing
    tumor must attract new blood vessels to fed
    itself. Eventually, many tumors metastatize
    pieces break off an move through the blood to new
  • Cancer treatments suffer from natural selection
    if you kill almost all the tumor cells but leave
    a few resistant cells alive, they multiply and
    the tumor grows back, now resistant to the
    therapy you applied.
  • Different cell types become cancerous in
    different ways, making a general cancer treatment
  • However, most cancer treatments (chemotherapy and
    radiation therapy) focus on stopping cell
    division. Common side effects like nausea, joint
    pain and hair loss are due to cell division
    stopping in other tissues.

Vinca Alkaloids
  • The Madagascar periwinkle Catharanthus roseus
    (used to be Vinca rosea) was used as a
    traditional Chinese remedy for diabetes. In the
    1950s it was tested scientifically, and it had
    little effect on diabetes. However, the
    scientists noticed that it suppressed bone marrow
    activity. This led to the finding that the
    lifespan of mice with leukemia was significantly
    prolonged by Vinca extracts. Vinca contains
    over 70 different alkaloids, but purification
    work isolated vincristine and vinblastine as the
    active agents.
  • These drugs prevent cell division by binding to
    the mitotic spindle, the apparatus that pulls the
    chromosomes apart. It binds to the spindle
    proteins, preventing them from joining together.
  • They are very useful in treating leukemia, which
    is cancer of the bone marrow cells that produce
    blood cells. It also helps with several other

  • Taxol is an alkaloid derived from the Pacific yew
    (Taxus brevifolia), a gymnosperm that grows in
    western North America.
  • In the 1960s, the National cancer Institute ran
    a large scale anticancer screening program. Most
    samples submitted were synthetic compounds, but
    there was also a program for screening natural
    products isolated from plants and fungi. Bark
    from the Pacific yew had some activity in a
    simple assay procedure.
  • Testing in animals and then humans showed that it
    helped with lung cancer, breast cancer, and
    ovarian cancer, as well as Kaposis sarcoma
    (common in AIDS).
  • Huge amounts of bark were harvested to purify the
    drug, increasing as it continued to show promise
    as a cancer treatment. It would be easy to
    drive the tree to extinction, since harvesting
    the bark kills the trees.
  • It is now produced from a line of tissue culture
    cells deriveed from the Pacific yew. The cells
    make and secrete taxol, which is them purified.
  • Taxol binds to the mitotic spindle and stabilizes
    the structure so it cant be re-used. This
    prevents further cell division.

Mitosis (Cell Division)