•malaria, leprosy, arthritis, dropsy, twilight sleep, cortisone, aspirin, prostaglandins ….

•ethnobotany, bioprospecting, and rain forest degradation •social and cultural aspects of healing shown by plant remedies

•comparison of healing styles•plants and religious activity•toxins and drugs•Doctrine of Signatures

M. KefferWaterloo-Oxford

may, 2001

Plants as biochemical factories

•phytoremediation, bioremediation, and Living Machines

•oxygenators and water purifiers for space travel

•genetic engineering and new uses for tobacco

Plants of economic importance•spices, flavourings, and trade

•coffee, tea, saffron, cinnamon, nutmeg, cloves and clove oil, coconut

• the Moluccas and the Spice Wars• industrials -- rubber, cotton

•rubber and World War II•structural materials: wood, palm

•lignins and structural strength•alternate food sources: algae

stay tuned for future presentations on:

ethnobotany

Ethnobotany 1• the study of plants learned from the people who

use them• often includes medicinal plants• often includes the study of indigenous peoples• research methods involve living with the people who use

the plants, and learning their methods from them

• in many cases the proper use of the plants is wrapped up with their everyday lives, and therefore difficult to explain to foreigners

• e.g. it’s hard to walk into the forest and find a cure for cancer when the local people don’t even have a word for cancer

• therefore foreigners like us must go to learn in THEIR environment, on THEIR terms.

threats to ethnobotanical knowledge• Threats include:

• expansion of “civilized” cultures into their habitat

• mining

• transport

• slash&burn agriculture• pollution

• attrition • (young members of tribes

leaving and not returning to learn from their elders -- no one to carry on the traditions)

Significance of ethnobotany• it’s not just the plants; it’s

• how they are used, • their preparation, • their admixtures, and • knowledge of fine differences between them

(closely related plants, plants that resemble each other at certain stages of the year)

• in most cases this knowledge is NOT written down ANYWHERE

• it is part of an oral tradition -- meaning it is only passed from person to person orally, through teaching

• not all peoples have writing • even if they did, for most, their secrets are

sacred and not to be told to just anyone

• Currently there are new diseases for which there is no known cure

• also some existing diseases have become resistant to antibiotics

• the forest may be the best place to learn about drug substances

• forests are disappearing, and with them, the people who know how to use these plants

• Note: an admixture is something added to the active ingredient to alter it in some way

• make it less toxic

• reduce its side effects

• increase its potency by allowing it to enter the bloodstream more quickly

• allow it to cross the blood-brain barrier

Malaria life cycle

• parasites live in gut of female Anopheles mosquito

• when mosquito bites, it injects fluid to act as anticoagulant and anaesthetic

• parasites enter human bloodstream

• travel to liver for another stage

• enter bloodstream and replicate in red blood cells

• burst the RBC when they reach large enough numbers and size

• when another mosquito bites, parasites move back into the mosquito gut to start the next round of replication

Malaria info from the WHO (World Health Organization)• Malaria kills more people than any other communicable disease except

tuberculosis• Caused by a protist parasite that lives both in mosquitoes and humans• since it is not a bacteria, antibiotics are NOT effective against it• it is curable if promptly treated• multi-drug resistant strains are now becoming more prevalent• major problem in areas covering 40% of the world’s population• symptoms:

•fever, shivering, pain in the joints, headache, repeated vomiting, convulsions, coma, severe anemia

•recurrent cycles of shivering and fever that coincide with the release of parasites within the blood

• kills over 3000 children per day worldwide -- far more than HIV• a single bout of infection usually costs the equivalent of 10 working days• ref: http://www.who.int/inf-fs/en/fact094.html

increased risk of malariaa hidden risk of global warming….?

cinchona• Malaria is the one of the top killers in the world• Evidence suggests it has been a concern at least

back to 500 BC• there were lots of “remedies” but no real cure • the Cinchona tree from South America

provided quinine• for several hundred years it was the only cure

• Significance:• At this time European colonialism was

expanding explosively into the Americas, Africa, India, Indonesia, and other areas of Asia.

• All these expansions were partially fuelled by the “discovery” of quinine

• Without it it is unlikely that expansion would have occurred nearly as quickly, since many colonialists were killed by malaria

leprosy• caused by mycobacterium similar to the

one that causes tuberculosis• infects and kills peripheral nerves

(extremities)• leads to numbness and lack of circulation• this often leads to gangrene or muscle

damage• nasal membranes also often infected - -

probably initial entry point of infection

leprosy 2• muscle wasting may cause bizarre contortion of joints

(first picture)• eyes also may be affected --

• nerves leading to cornea deteriorate; • therefore cornea and other membranes deteriorate

• cornea become numb, therefore don’t know when something’s in the eye

• leads to damage of membranes and eventual collapse of the nose and nasal tissue

• for further information check this link

social and historical implications of leprosy• dates to biblical times -- very old disease• lepers have traditionally been ostracized (booted out of

normal society) and forced to live in leper colonies• click here for further info on background

chaulmoogra• from an Indian tree• only thing found to be

effective for leprosy throughout history

• more recently replaced by dapsone (synthetic derivative)

• this was ONLY made possible by studying the active principle of the chaulmoogra plant

• currently there are many strains of M.leprae showing resistance to dapsone

• click here for more info• also check here for

specific details about the oil

cancer remedies

• Found in Madagascar• from the rosy periwinkle• periwinkle currently almost

extinct due to rainforest destruction

• vinblastine and vincristine have been isolated from this plant

• they are currently among the very few successful treatments for childhood leukemia

the original Salix

•Native people in North America chewed willow bark to relieve headache

•Willow bark is one source of salicylic acid

•Salicylic acid has similar pain-relieving and blood-thinning properties as aspirin

•However, it also tends to cause stomach upset, and lead to ulcers

•By chemically adding an acetyl group (CH3-CH2-) to salicylic acid it is changed to…

•AcetylSalicylic Acid (or ASA)

Willow blossom

prostaglandins• prostaglandins are secreted

by most animal tissues• wide array of activities

• stimulation or relaxation of smooth muscle

• dilation or constriction of blood vessels

• stimulation of inflammation responses

• enhancement of the perception of pain

• aspirin works by inhibiting the synthesis of prostaglandins

ASA and other pain relievers•ASA is still one of the best pain relievers for arthritis, muscle pain, etc.•lowers fever, relieves pain, reduces inflammation, and thins the blood•inhibits the formation of blood clots -- therefore used to reduce risk of stroke and CVAs (cardiovascular accidents)

•ASA is packaged into many different brands of “aspirin,” as well as cough meds, cold remedies, etc.

•The other two main pain relief medications available without a prescription are acetaminophen and ibuprofen -- both reduce prostaglandin action

•acetaminophen is the active ingredient in Tylenol and many other headache pills

•it has many of the same actions as ASA but does not tend to cause the same amount of gastrointestinal discomfort

•acetaminophen does not work as well for reduction of inflammation or blood thinning -- ASA is still the best balance of relief and lack of side effects

•acetaminophen is a coal tar derivative

“world’s worst diet”?

Camel blood

Camel milk

World’s worst diet 2

• This desert tribe survives on a frothed mixture of blood and milk.

• It provides all needed nutrients• but “should” produce a high blood

cholesterol level. • However, members of this tribe

regularly have among the lowest blood cholesterol levels of any group on earth

• Ethnobotanical research found that the members of the tribe add a type of bark to their mixture

• Further research suggests that this bark has blood cholesterol-lowering properties.

epena and shamanism

•This shows a shaman (herbal healer) and his apprentice at the start of a healing ceremony.

•Which one do you think is the shaman?•What do you think is happening in the picture, and why?

Epena and shamanism 2• Without diagnostic tools,

indigenous peoples have relied on spirit helpers to help them discover what is wrong with a sick person.

• Shamans (healers) also ask their spirits to help the sick person get better.

• In order to speak with their spirits, shamans often go into a trance

• certain drug substances are often used to speed up the process of entering the trance

• in the picture, the shaman is the one on the right.

• His assistant is blowing a powder, called epena, into the shaman’s nose

Within minutes, the shaman will be deeply entranced.

(The patient is not in the picture.)

Comparison of healing styles"western" medicine "traditional" medicine

Most diseases are caused bymicrobes

Most diseases caused byimbalance of natural levels, or

"bad spirits"Find offending organism and kill it Restore balance or drive out

bad spirit

Use diagnostic tests to discover thenature of the disease

Use divination or "vision" toassess disharmony -- must get

beyond the "normal"Mental status of patient usuallyseparate from disease process

Mental status of patient crucialto understanding disease

processEmphasis on diseases such as heart

disease, cancer,Emphasis on problems of skin,

digestive tract, problems due toinsects and animals

Western vs. indigenous pharmacopoeia

Note especially the differences for cardiovascular, cancer, and dermatology (skin)

connection with religion

Ancient Egyptian art showing a god pollinating a papyrus plant

Why would gods be associated with plants?

hunter-gatherers vs agriculturalists• for hunter-gatherer societies, plants were important but not as

important as the spirit of the animals on which they depended• when a society sees something as being extremely important, they

tend to deify it -- make it into a god in their art and culture• through this, we can learn about their culture by looking at their

religious art

• concept of sympathetic magic says that by portraying a thing, they can help to make it happen

•example: rain dance• with the agricultural revolution, people realized that their success

depended on their plants• stories involving gods were good ways to teach• plants in some cases offered routes to things beyond the normal

experience, and therefore became identified with gods

poppies

Opium and opiates• opium has been used for

centuries as a narcotic and a painkiller

• when research on brain chemicals began, it was found that the brain produces chemicals that “look” exactly like morphine

• the brain chemicals are called

endorphins• they are natural pain-killers• morphine has its effect because

it happens to have the same shape as the endorphins

• morphine and endorphins act as either hormones or neurotransmitters -- affecting the nerve cells they encounter

Research significance of drug substances• Understanding the structure of morphine

allowed understanding of the receptors in the brain through which morphine functions

• one way to understand a pathway is to find an example where the pathway DOESN’T WORK.

• Then look at the differences between the one that works and the one that doesn’t.

• neurotoxic plant substances show how pathways work by shutting down certain pathways -- they provide a case where the “normal” doesn’t work

• example: saxitoxin blocks sodium channels

Coca -- very different from cocoa

• Coca plant unmodified is an excellent source of calcium and vitamins

• many diets in the Andean highlands are deficient in calcium

• acts as a mild stimulant -- similar to strong coffee

• prevents fatigue and hunger

• excellent prevention against altitude sickness (common in the high altitudes of the Andes)

coca• Coca became a very

popular additive to drinks such as wine

• it is still included in Coca-cola• this is the only situation in

which it can be legally imported

• you won’t find it on the ingredients

• it’s allowed for it to be listed as a “natural flavouring.”

• many anaesthetics such as novocaine were created based on cocaine and its derivatives

Coca -- significance• important historical, social,

and religious significance• people feel that it connects

them to their land -- they see it as a gift, and to use it responsibly is their way of returning the gift

• also seen as sacred reaffirmation that they belong

• reminder from their gods to take care of the land

Coca -- VERY different from cocaine!• Coca leaves must be treated with strong acids to modify

the active ingredients into cocaine -- it is a long process that does NOT occur naturally under any circumstances

• many countries have destroyed wild coca growth, and coca plantations, in the attempt to cut down supplies

• these efforts are supported and promoted by the US “War on Drugs”

• this is in hope of reducing the amount of cocaine coming into the US… BUT:

• reduction in supply has the effect of increasing demand• probably does little to reduce the amount of coca

funneling through illegal routes• however, this does remove it from “natural” users • further info and source of pictures, click here.

calabar, witchcraft, and voodoo

Trial By Poison• Trial by Poison was a common way to test a

person who was suspected of lying• person would be given calabar beans, which

are TOXIC (due to the physostigmine)• person would become very sick, dizzy, would

foam at the mouth, and might die.• If the person died, they were obviously guilty• If they did not die, they must have been

innocent.

papaya• provides papain (meat

tenderizer)• also chymopapain (contact

lens cleaner and treatment for slipped discs)• Inject enzyme into problem

disk

• it dissolves the jelly in the disk

• This shrinks the disk and relieves pressure on the adjacent nerves

• reduces need for back surgery

Jimsonweed• also called angel’s

trumpet, or • Datura stramonium, or• thorn apple

• toxic -- to people and livestock

• may be hallucinogenic if properly prepared

• attractive flower with nice floral smell

• leaves have distinctive unpleasant odour when touched

“Jimsonweed”•called Jamestown weed according to legend that soldiers marching through Jamestown were treated to a lunch by the residents

•the soldiers spent the next few days variously on the rooftops, in the gutters, and wandering around in a “lunatic state.”

•most active ingredient is scopolamine

arthritis• Joint disorder that can effectively

cripple a person• immune system begins attacking

self tissue in the joints• joints become inflamed and sore• this calls even more

inflammatory cells• positive feedback cycle• joint surfaces become pitted and

misshapen• this further accelerates inflammation• many people have it and there is no cure• otherwise not damaging -- affected people must often live with

it for the rest of their lives• can prevent simple tasks -- like driving a car, holding the

phone, or opening the aspirin bottle

Arthritis and cortisone• 1930s: rheumatoid arthritis patients

showed dramatic improvement after jaundice • jaundice is liver disease -- leads to

yellowing of the skin and eyes; occurs as a symptom of some other disease, such as hepatitis

• also: arthritis would decrease during pregnancy, but come back after birth

• hormone called compound E found in both cases

• but compoud E was very difficult and expensive to synthesize

Cortisol and cortisone• Steroid hormone made

by the adrenal cortex

• causes: • increase in blood sugar

• increase in liver glycogen

• increased rate of conversion of protein into carbohydrate

• elevates blood sugar by conversion of non-carbohydrate molecules into glucose

adrenal gland

Cortisone: miracle cure for arthritis?• first test on humans: woman

with severe rheumatoid arthritis -- so bad she could hardly move

• previously, no treatment had shown any effect

• after three days of cortisol injections she could move easily

• after eight days of injections her symptoms were mostly “gone”

Cortisone: Overall Wonder Drug?

• Cortisone increased test animals’ resistance to cold, poisons, and other stresses

• Pneumonia symptoms would disappear, although the bacteria causing it was still there (remove the cortisone and the symptoms reappear!)

• tuberculosis symptoms would also disappear -- but bacteria still present also

• side effects: high blood pressure, excessive hair growth; mental problems; ulcers; brittle bones; fluid retention; obesity; mood swings

• Often abused! Athletes with joint injuries find that cortisone injections directly into the joint will reduce swelling and allow them to continue playing

• however, this usually leads to further damage of the joint

• also can lead to softening of the joint and permanent damage and disability

Mexican Yams, cortisone, and Dioscorea• In the 1930s and 40s, there

was an intense search for a plant source of cortisone

• none were found, but a vine called Strophanthus was found that could produce a substance that could easily be modified to provide cortisone

• however, this plant could not be cultivated outside its native jungle (not sure why)

• later it was found that certain Mexican yams (Dioscorea) could provide the same substance very cheaply

• this is the source of cortisone, progesterone, and estrogen for many birth control pills also

cortisone and progesterone

• note the similarities between the different substances

• for such similar molecules, they produce vastly different effects in the body!

plant toxins

Larger bar = more poisonousHuratoxin is more than 10 million times more toxic than cyanide

distance to herbs•Graph shows amount of walking time necessary for a particular healer to reach a forest large enough to find the plants he needs

•the time has increased greatly since 1940 due to forest being cut down in his area

may apple• podophyllotoxin for

cancer from the North American mayapple

Strophanthus vine• produces atropine

• also cortisone precursors

Digitalis (foxglove)•A relatively common disease in the 16th - early 20th

century was called dropsy•caused fluid retention in patients’ feet (swelling, also called edema)

• they also had weak hearts and often died of heart failure• it was found that an extract of foxglove would help clear up the disease

•foxglove was often grown in gardens for its pretty flowers

•“wise women” had known of this cure for a long time•but it didn’t become “valid” until an established (male) doctor started treating patients with it

•now known that foxglove contains digitalis•digitalis is, even now, one of our most important drugs for increasing the strength of the heart’s contraction

•dropsy occurred due to weakening of the heart -- therefore pumping was not strong enough, and fluids pooled in the lower limbs

Scopolamine (hyoscine)• Ophthalmic atropine, homatropine, and scopolamine are used to dilate (enlarge) the pupil of

the eye.• used before eye examinations, before and after eye surgery, and to treat certain eye conditions,

such as uveitis• obtained from plants of the nightshade family (Solanaceae), chiefly from henbane,

Hyoscyamus niger. • Structurally similar to the nerve substance acetylcholine• scopolamine acts by interfering with the transmission of nerve impulses by acetylcholine in

the parasympathetic nervous system• produces symptoms typical of parasympathetic system depression:

• dilated pupils • rapid heartbeat• dry skin, mouth, and respiratory passages

• Because scopolamine depresses the central nervous system, it is used as a sedative prior to anesthesia and as an antispasmodic in certain disorders characterized by restlessness and agitation, e.g., delirium tremens, psychosis, mania, and Parkinsonism.

• When combined with morphine, the effect produced is a tranquilized state known as

twilight sleep; this combination of drugs was formerly used in obstetrics but is now considered too dangerous.

• Overdosage of scopolamine causes delirium, delusions, paralysis, and stupor.

Solanaceae family (SOL-un-A-see-uh) (the Nightshades)

• The chief drug plants of the family are • belladonna, or deadly nightshade (Atropa belladonna), • henbane (Hyoscyamus niger)• mandrake (Mandragora officinum)• Jimson weed (Datura stramonium) (angel’s trumpet)• tobacco (Nicotiana tabacum).

• Many of the above were used in herbals and in magic potions• The family also includes several important food plants:

• potato (Solanum tuberosum) (note greens are poisonous, but not roots)

• tomato (Lycopersicon esculentum)• peppers (but not black pepper, which is a different family) • eggplant (Solanum melongena), (the only one native to the Old

World)

• Species of salpiglossis, petunia, butterfly flower, and the genus Solanum are among the members of the family cultivated as ornamentals.

Atropa (deadly nightshade)

Monk’s hood

Source of aconitine

curare• from strychnos plants

• these plants are the source of strychnine (rat poison)

• arrow poisons of many different tribes

• similar substance found in buttercups• “In preparing the arrow poison, the

seeds, deprived of their hairs, are pounded to a pulp, the adhesive sap of another plant is added, and the mixture smeared for 6 inches along the point of the arrow. Game wounded by such an arrow is said to be rarely able to move 100 yards, while the flesh can be eaten without bad effect.”

• (from encyclopedia.com)

•curare is a very important muscle relaxant for surgery•an adventurer tried the drug on their donkey -- no Westerners knew how the drug actually killed•they used a set of bellows to keep its lungs inflated (simulate its breathing)•the donkey survived after the drug wore off -- with no ill effects•drug works by paralyzing the muscles, including the breathing muscles•otherwise it does no harm at all to the body

Doctrine of signatures

•use of various plants was indicated by the form or shape of the plant.

•Concept was in wide use throughout the middle ages and Renaissance (ca. 800 - 1500 AD)

•based on much older belief:

“As Above, So Below.”•Things that happened in the heavens, and in nature, had influence on the affairs of humans

•God wanted to indicate the plant’s purpose to humans -- so that’s why they were shaped as they were.

BloodrootClick here for web link

•A blood red juice can be extracted from the reddish orange root

•The juice from the root was used as a body paint and dye by Native Americans.

•Warriors painted their faces with it

•produces a yellow-orange dye that is very fast (permanent)

•has flesh destroying properties •therefore good for treating conditions of the skin such as ringworm, warts, polyps, fungal growths

boneset

•long been used to treat fevers from simple colds to typhus.

•tea often used as a diuretic•leaves of E. perfoliatum were once considered useful in mending broken bones

•belief probably came from observation of the fusion of the leaves at their bases

•does have some toxic properties

•toxic propterties had nothing to do with healing, but led people to believe in its effectiveness

note fusion of leaves

hepatica

guess what people used this plant for….

same

Other notes• Fishing and the source of

rotenone• admixtures that are not

necessarily “active” ingredients, but that may increase toxicity or reduce side-effects

• frankincense• cassava beer, bread• role of “modernization” --

increased skin infections due to western clothing and also to discouragement of plant remedies as “un-Christian”

• Zoopharmacognosy:• elephant herbs• monkey soil• the spirit of the Great Bear

• “Snake Oil” and “Indian Elixir”• as people moved west across North

America, they learned many herbal remedies from the native people

• soon, anything that appeared to have come from a Native recipe was considered to be good

• “entrepreneurs” took advantage of this and began selling “Indian Elixir” on every corner -- often with absolutely no connection to any Native recipes