Medicinal Plants

Prehistoric times

• No one knows where or when plants first began to be used to treat disease
• Accidental discovery of some new plant food that eased pain might have been the beginning of folk knowledge
• Early evidence: the grave of a Neanderthal man buried 60,000 years ago. Pollen analysis indicated that plants buried with the corpse were all of medicinal value

Recorded history

• Earliest record 4,000 year old Sumerian clay tablet recorded numerous plant remedies
• Ancient Egyptian civilization had a wealth of information on medicinal plants - Ebers Papyrus 3500 yrs ago

Ancient China

• The Pun-tsao, a pharmacopoeia published around 1600, contained thousands of herbal cures that are attributed to the works of Shen-nung, China's legendary Emperor who lived over 4500 years ago

Ancient India

• Herbal medicine dates back several thousand years to the Rig-Veda, the collection of Hindu sacred verses
• This is the basis of a health care system known as Ayurvedic medicine
• One useful plant that has come from Ayurvedic tradition is snakeroot, Rauwolfia serpentina

Foundations of western medicine

• These ancient records indicate that in all parts of the world native peoples discovered and developed medicinal uses of local plants
• Herbal medicine of ancient Greece laid the foundations of our Western medicine

Ancient Greek and Roman medicine

• Greek physician Hippocrates (460-377 B.C.), known as the Father of Medicine used various herbal remedies in his treatments
• Roman physician Dioscorides (1st century A.D.) wrote De Materia Medica which contained an account of over 600 species of plants with medicinal value.

De Materia Medica

• Descriptions of plants, directions on the preparation, uses, and side effects
• Many still in use
• willow bark tea - precursor to aspirin
• Some have been lost
• Greek and Roman women used silphium as an effective contraceptive for 1,000 yrs - now extinct
• Standard medical reference for 1500 years
• Little new knowledge was added in Europe during the Dark Ages

Age of herbals

• Beginning of Renaissance in the early 15th century saw a renewal of learning
• Botanically - revival of herbalism for medicinal plants
• Coupled with the invention of the printing press in 1440 ushered in the Age of Herbals

Herbals

• Beautifully illustrated books that described plants
• When to collect, useful parts
• Medicinal and culinary uses
• Also included a lot of misinformation and superstition
• Often advocated the Doctrine of Signatures

Doctrine of Signatures

• Medicinal use recognized by distinct "signatures" visible on the plant which corresponded to human anatomy
• Red juice of bloodwort to treat blood disorders
• Lobed appearance of liverworts to aid the liver
• Belief in this concept developed independently among different cultures

18th Century

• As science progressed, a dichotomy in medicine developed between practitioners of herbal medicine and regular physicians
• About this same time a similar split occurred between herbalism and scientific botany

Path to modern medicine

• Many herbal remedies had a sound scientific basis
• Some became useful prescriptions drugs
• William Withering was the first to scientifically investigate a folk remedy
• His studies (1775-1785) of foxglove to treat dropsy (congestive heart failure) set standard for pharmaceutical chemistry

19th Century

• Scientists began purifying the active extracts from medicinal plants
• Breakthrough in pharmaceutical chemistry came when Serturner isolated morphine from opium poppy in 1806
• First synthetic drugs were developed in the middle of the 19th century based on natural products

20th Century

• Direct use of plant extracts continued to decrease in the late 19th and 20th centuries
• Today medicinal plants still contribute significantly to prescription drugs
• 25% of prescriptions written in the U.S. contain plant-derived active ingredients
• 50% if fungal products are included
• An even larger percent based on semi-synthetic or wholly synthetic ingredients originally isolated from plants

Late 20th century

• Renewed interest in investigating plants for medically useful compounds
• Recent success of taxol from the Pacific yew tree has shown this interest is worth pursuing

Herbal medicine today

• 75%-90% of the rural population in developing nations rely on herbal medicine as their only health care
• Medicinal herbs are sold alongside vegetables in village markets
• Practitioners of herbal medicine undergo extensive training to learn the plants, their uses, and preparation of remedies

People's Republic of China

• Traditional herbal medicine incorporated into a modern health care system
• Blend of herbal medicine, acupuncture, and Western medicine
• Thousands of species of medicinal herbs are available for the Chinese herbalist
• Chinese apothecaries contain an incredible assortment of dried plant specimens
• Prescriptions filled with blends of specific herbs

India

• Traditional systems separate from Western medicine
• At universities medical students are trained in Western medicine
• Most people use traditional systems:
• Ayurvedic medicine - Hindu origin
• Unani medicine - Muslim and Greek origin
• Economics also a factor - manufactured pharmaceuticals too expensive for most

Other areas

• Interest in medicinal plants has focused on indigenous peoples in many parts of the world
• Ethnobotanists are spending time with local tribes and learning their medical lore before they are lost forever
• Especially important among native peoples in the tropical rain forests

Tropical rain forests

• Widespread destruction threatens to eliminate thousands of species that have never been scientifically investigated for medical potential
• Erosion of tribal cultures is also a threat to the knowledge of herbal practices
• As younger members of native groups are drawn away from tribal lifestyles, oral traditions are not passed on

Active principles in plants

• Secondary plant products
• Two major categories of these compounds
• alkaloids
• glycosides
• Other types of compounds are also important - essential oils

Alkaloids

• Diverse group of compounds
• Over 3000 have been identified
• Most occur in herbaceous dicots and fungi
• Three families that are particularly known for their alkaloids: Fabaceae (legume family), the Solanaceae (nightshade family) and the Rubiaceae (coffee family)

Chemistry of alkaloids

• Vary greatly in chemical structure
• Alkaloids share several characteristics:
• they contain nitrogen
• they are usually alkaline
• they have a bitter taste

Physiological effects of alkaloids

• Diverse effects with the most pronounced on the nervous system
• Can also have psychological effects
• Some medicinally important, some psychoactive, some poisonous
• Often a fine line between a medicinal and toxic dose
• Common alkaloids: caffeine, nicotine, cocaine, morphine, quinine, ephedrine

Psychoactive Compounds

• Affect the central nervous system - often by influencing neurotransmitters
• Categories of psychoactive cmpds
• Stimulants
• Hallucinogens
• Depressants
• May also be narcotic

Narcotic Compounds

• By definition a narcotic drug induces central nervous system depression resulting in numbness, lethargy, sleep
• In current use, a narcotic is a psychoactive drug that is dangerously addictive
• Addictive cmpds elicit: psychological dependence, physiological dependence, and/or tolerance

Glycosides

• Also widespread in the plant kingdom and second in importance as medicines or toxins
• Have sugar molecule (glyco-) is attached to the active component
• Active portion variable, sugar is glucose
• Generally categorized by the active component: cyanogenic glycosides, cardiac glycosides, and saponins.

Cyanogenic glycosides

• Release cyanide (HCN) upon breakdown
• Cassava contains cyanogenic glycosides
• Seeds, pits, and bark of many members of the rose family (apples, pears, almonds, apricots, cherries, peaches, and plums) contain amygdalin, a cyanogenic glycoside

Amygdalin

• Apricot pits are rich in amygdalin
• Ground up for preparation of laetrile, a controversial cancer treatment
• Theoretically, laetrile releases HCN only in the presence of tumor cells and selectively destroys them
• Not proven and laetrile not approved for cancer therapy in the United States

Cardiac glycosides

• Steroid molecule is active component
• Cardiac glycosides effect the contraction of heart muscle
• In proper doses, some are used to treat various forms of heart failure
• Best known is digitalis
• Some of the deadliest plants, such as milkweed and oleander, contain toxic levels of cardiac glycosides

Saponins

• Steroid molecule is active component
• Can be highly toxic causing severe gastric irritation and hemolytic anemia
• One useful saponin is disogenin from yams (Dioscorea spp.) which can be used to synthesis various hormones such as progesterone (ingredient in birth control pills) and cortisone

Some important medicinal plants

• Foxglove - heart disease - digitalis
• Willow bark tea - pain, fever - aspirin
• Fever Bark Tree - malaria - quinine
• Snakeroot - hypertension - reserpine
• Aloe - burns - various glycosides
• Vinca - leukemia - vincristine
• Taxus - ovarian & breast cancer - taxol

Foxglove and heart disease

• Foxglove - Digitalis purpurea
• Extract called digitalis
• Long history as a folk remedy for congestive heart failure (dropsy)
• William Withering investigated this remedy from 1775-1785 - first scientific study of a medicinal plant

Digitalis purpurea

• Purple foxglove - an attractive biennial with large purple bell-shaped flowers
• Often used as a garden ornamental
• Leaves contain over 30 cardiac glycosides with digoxin and digitoxin the most medically significant
• Concentration of glycosides highest before flowering
• Leaves dried, powdered, then extracted

Foxglove

​

Digitalis purpurea

Physiological action

• Digitalis slows heart rate and increases strength of each heartbeat
• Results: more blood is pumped with each contraction
• Improved circulation, decreases edema, and increases kidney output
• Effective treatment - not a cure
• Fine line between a therapeutic and toxic dose of digitalis

Aspirin: willow bark to Bayer

• Most widely used synthetic drug but origins are botanical
• Bark of willow trees (Salix spp.) used by many cultures for reducing fever and relieving pain - in form of a tea

Path to a synthetic

• In 1828 salicin was first isolated and over the next decade the extraction method was refined
• Salicin is a glycoside of salicylic acid
• Salicylates occur widely in species of Salix as well as many other plants including meadowsweet (Spirea ulmaria)

Next step

• Laboratory synthesis of salicylic acid in the mid-19th century
• Salicylic acid was an inexpensive treatment for many ailments - rheumatic fever, gout, arthritis
• Had side effects - especially gastric
• In 1898 Felix Hoffman, a chemist at Bayer Company came across acetylsalicylic acid

Acetylsalicylic acid

• Effective and more palatable
• Soon given the name aspirin
• "a" is from the acetylsalicylic acid and the
• "spirin" from Spirea the plant from which salicylic acid was first isolated

Physiological action

• Three classic properties
• anti-inflammatory
• antipyretic (fever reducing)
• analgesic (pain relieving)
• New uses in the prevention of heart attacks, strokes, and colon cancer
• Drawbacks:
• irritates the stomach
• Reye's syndrome

Malaria and fever bark tree

• Malaria known since antiquity, is still the world's most prevalent disease
• 2 to 3 million people die each year from malaria, and at least one million of these deaths are young children
• Today malaria largely confined to tropical and subtropical countries in Asia, Africa, South America, and Central America

Malaria

• Caused by unicellular parasites in genus Plasmodium
• Spread by bite of Anopheles mosquito
• Parasite multiplies in liver and released in blood stream
• Invade red blood cells - multiply and rupture RBC
• Cycle repeats every few days -symptoms fever, chills, anemia....death

Fever bark tree

• Native to the eastern slopes of the Andes Mountains
• Called quina-quina by the Incas
• Several species of Cinchona
• Small evergreen trees belong to the Rubiaceae, the coffee family
• Fever reducing powers of the tree were well known to the Incas who shared knowledge with Jesuit missionaries

Jesuit’s bark

• Jesuits used bark to treat people with malaria
• In 1638 - Countess of Cinchon, wife of the Viceroy of Peru - miraculous recovery spread reputation of the bark
• Years later Linnaeus named the genus Cinchona in honor of the countess
• By the end of the 17th century the powdered bark of the quina-quina tree was the standard treatment for malaria

Quinine

• In 1820 two French scientists isolated the alkaloid quinine
• Within a few years purified quinine was available commercially
• Demand for the bark increased even more
• 36 alkaloids in Cinchona bark - 4 have anti-malarial properties
• Quinine is the most effective

Synthetics

• During World War II synthetics were developed
• Today the most widely used drug for malaria is chloroquine which is less toxic and more effective than quinine
• Widespread use of chloroquine has resulted in chloroquine-resistant strains of the parasite
• Quinine used for these infections in combination with other drugs

Physiological action

• Quinine kills parasite in blood stream
• Also effective as a prophylactic to prevent initial infection of red blood cells in travelers
• "gin and tonic"
• Recently scientists have been investigating anti-malarial properties of weed Artemesia annua, wormwood

Snakeroot, schizophrenia, and hypertension

• Snakeroot, Rauwolfia serpentina
• "doctrine of signatures"- because long coiled roots resembled a snake, healers believed that the root could be used for treating snake bites
• For over 4000 years, Hindu healers used the root for the treatment of snakebites, insect stings, and even mental illness

Rauwolfia serpentina and reserpine

• In 1952 the alkaloid reserpine was isolated from the roots
• Later dozens of alkaloids found
• The sedative effects of reserpine made it valuable as a tranquilizers - side effect was a reduction in blood pressure
• Today, this is actually the principal application of reserpine, as a treatment for hypertension

Burn plant - Aloe vera

• Well known folk remedy is use of Aloe vera sap for minor burns
• Used for thousands of years as treatments for various skin ailments
• Aloe vera (A. barbadensis) the best known member of the genus but other Aloe species also used

Aloe leaves

• Thick mucilaginous sap
• Soothing effect on injured skin
• Numerous compounds including several anthraquinone glycosides collectively referred to as aloin
• Chrysophanic acid also present - possibly the compound with the greatest healing effect on skin

Action

• Sap promotes faster healing with less scaring by stimulating cell growth
• Inhibits bacterial and fungal infection
• Compounds in the sap inhibit pain, itching, and inflammation
• In recent years the cosmetic industry has capitalized on the moisturizing effects of the sap and it can be found in a variety of skin creams, shampoos, sun screen lotions, and bath oils

Cancer therapy

• Cancer is a diverse group of diseases characterized by uncontrolled growth of abnormal cells.
• Today in the United States cancer is the leading cause of death
• Search for cancer cures is relentless
• Plants have figured prominently in folk remedies for cancer
• Over 3000 plant species had been used

Search for drugs

• In the late 1950's National Cancer Institute and USDA began search for plants with anti-cancer properties
• Thousands of plants have been scientifically screened, and several have become standard chemotherapy for different forms of cancers
• Search is not over since only a small percentage have been screened

Vinblastine and vincristine

• Treatments for leukemia and lymphoma
• Alkaloids from Madagascar periwinkle, Catharanthus roseus (Vinca rosea)
• Used by traditional healers as treatment for diabetes

Screening

• Investigating this claim in the 1950's, scientists at the University of Western Ontario in Canada and Eli Lilly Pharmaceuticals in Indianapolis found no evidence of usefulness in treating diabetes
• Extracts from the leaves were found to be effective against leukemia cells and
• Alkaloids responsible were identified

Use today

• Vincristine and vinblastine major chemotherapeutic agents
• Vincristine has been especially effective for treating acute childhood leukemia, often with 99% remission rates
• Vinblastine has been especially effective for treating Hodgkin's disease
• Both alkaloids also used for other types of cancer

Pacific yew trees and taxol

• Taxol obtained from the bark of the Pacific yew, Taxus brevifolia
• Anti-tumor properties were first discovered in the 1960's during the screening program of the National Cancer Institute
• Taxol - only recently approved
• Clinical trials showed taxol especially promising in treating ovarian and breast cancer

Taxus - yew

Supply of taxol

• Original from bark of mature Pacific yew trees, a slow-growing conifer of old-growth forests in the Pacific NW
• Concern about destruction of ancient forests
• New sources
• Other species of Taxus contain taxol
• Tissue cultures of bark cells promising
• Recently synthesized in the laboratory

What’s in the future

• Search for medicinal plants continues
• Especially in tropical rain forests
• Time is critical before plants are lost and cultural knowledge of the plants are lost
• Same is true among native peoples everywhere includes Native Americans