BSCI 124 Lecture Notes

I. Introduction

• A. Plants are inventive chemists - more so than us animals
  B. Some may be nutritious, poisonous, hallucinogenic or therapeutic.

II. History of Drugs from Plants [An excellent review! see also this site for the history of medicine]

• A. Early use
  • 1. Assyrian herbal of 7th century B.C. gives list of medicinal plants
    2. Chinese emperor Shen Nung (2800 B.C.) described use herbal medicines
    3. Ebers medical papyrus from Egypt arranged medicinal plants in 1550 B.C.
    4. The ancient Greeks studied medicinal plants for centuries, and Dioscorides wrote De Materia Medica (Latin title of Greek work) in about 75 BC. Manuscript detailed some 600 botanicals. Authoritative reference concerning medicinal plants for the next 1500 years! Earliest extant manuscript copied around 512, some 400 pages of colored paintings
    5. Tang Shen-wei publishes (by movable type) 31 books on medicinal plants in 1108
    6. Islamic and Indian physicians wrote numerous works prior to 1100 A.D.
    7. Most of the early manuscripts preserved by the Arabs; Cordova, in Moorish Spain, the capital of scientific knowledge in eighth century.
    8. See examples of works preserved in the Vatican Library

  B. Age of Herbals (1488-1682)

  • 1. Herbals
    • a. Printed book from movable type began around 1440.
      b. First herbal written in 1488; an illustration from an early herbal by Otto Brunfels published at the time of his death in 1534
      c. Most filled with superstition; maintained useful information, mostly on medicinal plants.
      d. Major herbalists were Conrad Gesner, Leonhard Fuchs, Hieronymus Boch, William Turner, John Gerard and Nicholas Culpeper. Gerard's The Herball [REQUIRED READING] and Culpeper's books were used in America
      e. John Parkinson, who died in 1650, was the last of the herbalist in England; his book also was widely used in the American colonies.

    2. Doctrine of signatures [REQUIRED READING]: Part of a plant had the shape of a part of the human body, it would be useful in treating a disease of the human part it most closely resembled.

    • a. Walnuts treat brain disorders
      b. Hepatica with its kidney-shaped leaves for kidney diseases

    3. Most herbalists were both physician and botanist, the two fields not diverging until the mid 1700s.

    • a. Physicians followed Dioscorides in the Mediterranean region of Europe
      b. German and Dutch physicians consulted witches (aka women) in expanding their knowledge of medicinal plants beyond Dioscorides

    4. Discovery of numerous valuable medicinal plants in the New World did much to free early medicine from superstitions.
    5. Use of folk medicine continues to the present day in many societies and cultures with many plants still in common use

III. Novel Chemicals in Plants

• A. Two theories account for the variety of chemicals found in plants
  • 1. Chemicals for survival -- the evolutionary strategy
    • a. Protection from herbivory and predation - chemical (e.g., compounds) and mechanical (e.g., thorns)
      b. Allelopathy - plants secrete toxins from their roots that prevent the germination of plants in their root zone; this reduces competition

    2. Chemicals by accident -- the random strategy

    • a. No excretory system so compounds accumulate
      b. With neutral selection pressure, compounds accumulate, there being pressure neither for their retention nor their loss.

IV. Human Dependence on Drugs from Plants

• A. Over 25% of our common medicines contain at least some compounds obtained from plants.
  B. In US approximately 10% of our major drugs have plant extracts as their active ingredient.
  C. In less developed countries the World Health Organization estimates that 75-80% of the people rely on plant-based medicines for primary health care.

V. Role of Synthetic Drugs

• A. Useful plant compounds are often easy to synthesize.
  B. No dependency on plant collectors or growers as a source or the long-term survival of the plant.
  C. In some instances we do not know how to synthesize the desired compound, in other instances it is cheaper to collect from natural sources.
  D. Synthetics can be patented; natural compounds can not - it is a question of dollars.

VI. Plant-based Drugs in Use

• A. Alkaloids: Over 5,000 alkaloids have been identified in numerous plant families, most in the angiosperms.
  • 1. Chemical structure (ibogaine: an alkaloid from an African plant used to reduce cocaine withdrawal symptoms; courtesy of The Ibogaine Dossier) ---->
    2. Properties
    • a. contain nitrogen
      b. are alkaline or basic in reactions
      c. taste bitter
      d. have a physiological effect on animals, usually working on nervous system
      e. the names of most alkaloids end in "...ine" such as: morphine, quinine

    3. Importance to humans

    • a. Source mildly addictive drugs (caffeine)
      b. Addictive compounds in our drugs (cocaine or nicotine)
      c. Poisonous toxins (strychnine)
      d. Pain killers (codeine and morphine)
      e. Important cures (malaria and quinine)

  B. Representative Plants Producing Alkaloids as Drugs

  • 1. Opium poppy (Papaver somniferum): morphine and codeine
    • a. Annual, native to Turkey and Asia Minor, produces a latex-filled capsule, and this milky sap is the source of opium, which contains a mixture of 26 alkaloids>
      b. Morphine isolated in 1806; morphine is 10% opiate, codeine is 1%.
      c. Heroin is a concentrated form extract of opium; a major drug in the United States.

    2. Cinchona tree or Peruvian bark (Cinchona succirubra): quinine (also here)

    • a. Malaria has killed more people than all our wars put together, one of the oldest recorded diseases
      b. The alkaloid quinine is produced in the bark; native of the Andes in Peru and Bolivia. First used by native peoples against malaria, but it wasn't until the 1600s that news of a cure for malaria reached Europe. Knowledge suppressed because it was used by the "heathens"; wife of Spanish official treated with cinchona proved its effectiveness
      c. Quinine gives tonic water its characteristic bitter taste - hence the popularity of gin and tonic in tropical areas of the British Empire
      d. Modern quinine comes from chemically related synthetic compounds; renewed interest in natural quinine as some strains of plasmodium are resistant

    3. Mandrake (Mandragora officinarum ---->): Compound: Contains several alkaloids including atropine, scopolamine, podophyllin, mandragorin and hyoscyamine

    • a. An anesthetic alkaloid, used to deaden pain goes back to the Old Testament
      b. Used as an instrument of war - because it both deadens pain and is sleep-inducing, it is written that Hannibal triumphed over African rebels by staging a fake retreat leaving behind mandrake to stupefy his enemies, after which he returned to slaughter them easily. Supposedly Caesar used same ploy
      c. Shape of mandrake: The root frequently forks with two leg-like branches and sometimes a protuberance that suggests male genitals; hence the name mandrake (man + dragon = potent male)
      d. According to Doctrine of Signatures makes men virile; hardly a good aphrodisiac as it puts you to sleep!

    4. Belladonna (Atropa belladonna): atropine and scopolamine]

    • a. In use since the Middle Ages
      b. The common name, "belladonna" or "beautiful lady" refers to the ancient practice by Italian and Spanish women of putting sap in their eyes to enlarge the pupils - to achieve a seductive look
      c. Used still by opthamologists
      d. Atropine and scopolamine have many other uses - they stimulate the sympathetic nervous system - they are used with palsy, to stimulate circulation, and in some 50 other conditions
      e. The related jimson weed (Datura spp.) is frequently used by unknowning children; while it will cause hallucinations, it can also kill!

    5. Ipecac (Cephaelis ipecacuana): emetine

    • a. Herbaceous perennial from Central and South America with an unusual flower
      b. The alkaloid acts as an emetic: makes you throw up "ipecac" was developed by a pirate -- something good to do if you have been poisoned!

    6. Tobacco (Nicotiana tabacum): nicotine

    • a. Native of the New World, first introduced for its supposed medicinal value in 1614 by John Rolfe, an associate of Sir Walter Raleigh. In the 17th and 18th centuries it was recommended to cure dozens of illnesses - everything from cancer to the common cold
      b. The botanist John Hill was the first to associate tobacco use with cancer, reporting, in the 1791, that snuff caused nasal cancers
      c. A contact poison to most insects, an important insecticide

    7. Coffee (Coffea arabica) and tea (Camelina sinensis): caffeine

    • a. Coffee: native of northeastern Africa around Ethiopia. Alkaloids are in the fruits
      b. Used medicinally for centuries has an effect on blood pressure, pulse, and other functions
      c. Tea: native to China and India; probably used first medically effects similar to that of coffee

  C. Glycosides: chemical compounds consist of one or more sugar molecules (usually glucose, hence the name) attached to one or more non-sugar molecules

  • 1. Properties: Often bitter; marked physiological effect on animals; important in medicine
    2. Cardiac glycoside: a medicine that stimulates the heart
    3. Example: Digitalis or foxglove (Digitalis purpurea): Digitoxin ---->
    • a. Native of Europe, long in use; common garden plant; leaves are used as a heart stimulant
      b. Excessive dose can be fatal, extremely toxic. Don't chew the leaves!

    4. Example: plantain (Plantago major): aucubin

    • a. World-wide weed
      b. Used to discourage smoking

    5. Example: Colocynth or wild gourd (Citrullus colocynthis): elaterin

    • a. North Africa to tropical Asia
      b. Used as a drastic purgative; in use since biblical times

    6. Example: Rose relatives (Prunus, Amygdalus): characteristic scent of almond extract highly poisonous.
    7. Special example: ginseng or ren shen (="man essence") (Panix ginseng or P. quinquefolia): ginsenosides or panaxosides [REVIEW!] - concentrated in roots

    • a. Panax ginseng: <---- Native of China, southeastern Russia, Korea and Japan
      b. Widely cultivated; very expensive, $200/lb for whole roots; usually considered a restorative plant by the Chinese
      c. Considered a "cure-all" by many; the human-like root usually used; a plant even of festivals
      d. Panax quinquefolia (see illustration below): Native to eastern North America
      e. Used by American Indians only after informed of its medical value to Jesuit missionaries in the 1500s. Daniel Boone made more money collecting and selling ginseng than from trapping and selling furs!
      f. Exported from the United States and Canada since colonial days; rare in the wild and though widely cultivated, the plant is still expensive; a $200 million a year business
    • g. Wild plants are more valuable that cultivated ones
      h. Ginseng found in a variety of products (drinks including various soft drinks, beer, pills, tonics, with honey and/or bee pollen, liquid syrup(powders, chips or whole roots), especially as a sexual tonic for men; numerous claims are made, but few documented. Ginsana, a dietary supplement, is the best known American product.
      i. Minor correction: American ginseng was originally collected by John Banister of Virginia in the 1680s; it was also noted in Maryland in the 1690s. Its significance was not noted until the English sea captain, Cunningham, returned from China in 1700 with information about the plant.

VII. Future Drugs in Plants

• A. Current knowledge
  • 1. About 10% of the over 250,000 species of plants have been extensively screened in laboratories to determine their therapeutic potential
    
    • a. Examples: Camptotheca (Camptotheca acuminata), a traditional Chinese anticancer plant, the source of camptothecin. This drug has just been approved for use
      b. Mayapple (Podophyllum peltatum), a native American plant (see image ---->) and the source of podophyllotoxin. Etopiside, also isolated from Podophyllum, was worth $350 million in 1993
      c. Yew (Taxus brevifolia and T. baccata), a Pacific Northwest native tree, is the source of parclitaxel, better known by the commercial name "taxol", had sales worth $600 million in 1995
      d. Other anticancer plants

    2. Approximately 120 plant-based prescription drugs are on the market, and these drugs come from only 95 different species of plants
    3. National Cancer Institute has expanded its testing program for natural products, and drug companies send out botanists to collect plants in the major rain forests of Asia, Africa and the Amazon
    4. Many of our drugs have come from tropical plants. 25% of the world's plants are found in the tropical Amazon alone
    5. Two major problems:

    • a. Tropical rainforests are currently being destroyed or degraded faster than any other biome
      b. Shamen and witch doctors who have knowledge of plants are disappearing. Young Indian boys are not interested in what they perceive as old fashioned ideas and so the knowledge is not being passed on, but dies with the medicine men

  
  

  "Every time a medicine man dies it is like a library burning down" Mark Plotkin, ethnobotanist

  
  
  

VIII. The Problem of Ownership

• A. Intellectual Property Rights: Who owns the plants, its chemicals, its genes - none of these questions have been solved via international agreement
  B. The rosy periwinkle(Catharanthus roseus) is native to Madagascar. From this plant we have isolated two alkaloids (vinblastine and vincristine) - one that combats Hodgkins Disease, and another used to treat childhood leukemia. The annual sales of these drugs is over $100 million (and has done so for more than 30 years) - none of this goes back to Madagascar, one of the world's poorest countries
  C. Some drug companies have entered into agreements with certain countries to survey their plants for unique compounds. Can a naturally occurring compound be patented? Without patent protection why should a company go to the expense of developing the compound commercially?
  D. Is it worth it? Steroids, which trace their development back to wild yam, at one time commanded some 15% of the world's pharmaceutical market, today their annual share of that $150 billion a year market is less and most are derived as a by-product of soybean production

IX. Herbal Medicines

• A. Definition:
  • 1. Naturally occurring therapeutic compounds in biological organisms; classified as food supplements rather than drugs because herbal companies that say they cannot afford the clinical testing required by the FDA for drugs
    2. Manufacture drugs are pharmaceuticals; pharmaceuticals are regulated by the Food and Drug Administration (FDA)
    3. Drug companies typically spend $100 million to test a prescription drug for federal approval, and $50 million on tests for over-the-counter drugs; costs can be recoup only by patenting the products
    4. Herbal alone can not be patented

  B. Use: 75-80% of the world's population depends on traditional herbal medicine
  

  • 1. Herbs and their uses

  C. Safety

  • 1. Unregulated herbal products can be removed from the market if they are shown to be unsafe
    2. Sales of herbal products have been increasing, today they are a $1.5 billion industry
    3. Until a year ago there was no central registry for deaths and injuries caused by the ingestion of herbals; such a list is being kept by the FDA
    4. No ongoing testing in the US to provide consumers with precise information on herbal medicines

A recipe for abortion in a popular herbal guide for women suggests using the herb pennyroyal (Mentha pulegium). In 1994 Kurt Cobain popularized a song "Pennyroyal Tea." It is commonly found in health food stores, and most of us assume there is nothing in a health food store would can kill us. Nevertheless, a college student in California died a slow and painful death last year trying to induce a "natural" abortion using pennyroyal in spite of numerous published warnings. BE CAREFUL, NEVER TAKE ANY PLANT COMPOUND UNLESS YOU KNOW IT IS SAFE!

Always be careful.

Other sites of interest:

The following sites are examples. There is no intent to endorse any site or point of view regarding alternative medical practices or sources of information.

Medical Plants: A Review!
"Cancer-killing plants" by Bryan Ness
Alternative Medicine Sites from Yahoo
Alternative Medicine Online Sources
Native American traditional herbal & plant knowledge
Bibliography of Medicinal and Useful Plants
Botanical.com: Includes a Modern Herbal
Ethnobotanical Uses of Plants
Herbs as Medicine: An excellent set of links
Herb, Spice and Medicinal Plant Digest
HerbWeb
Phytochemical and Ethnobotanical databases: Maintained by USDA and James A. Duke
Poisonous Plant Database (bibliography
Plants for a future
Cyberbotanica: Plant and Cancer Treatments
Shamanism
Alternative Medicines: A summary of the many treatments; a good review!
AIDS Alternative Treatment Page
Chinese Acupuncture
Herb Research Foundation
Chinese Herbology
Ginkgo extract- commercial website
Holistic Medicine
Homeopathy Home Page
Southwest School of Botanical Medicine
The Herbal Encyclopedia: A valuable resource
Herbals and Early Gardening Books
The Cigarette Papers
History of cigarettes in the United States

Still have a question regarding medicinal plants? Ask Dr. James A. Duke, noted ethnobotanist and leading authority on medicinal plants.

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Last revised: Oct 16, 1998 - Straney