Walk into any pharmacy in the U.S., Canada, or Western Europe today and ask to examine a bottle of prescription medicine chosen at random and there is a 1 in 4 chance that the medicine you hold in your hand has an active ingredient derived form a plant.
1. 25% of all modern Western medicines employ at least 1 active plant ingredient.
2. And that % is considerably higher elsewhere in the world, where it has been estimated that 80% of the world’s inhabitants rely on traditional medicine for their primary health care needs.
It is uncertain where or when plants first began to be used in the treatment of disease, but the connection between plants and health has existed for thousands of years.
Evidence of this early association has been found in the grave of a Neanderthal man buried 60,000 years ago. Pollen analysis indicates the numerous plants buried along with the corpse were of medicinal use.
The earliest known medical document is a 4,000 year old Sumerian clay tablet that recorded plant remedies for various illnesses.
The ancient Egyptians were prescribing mandrake (Mandragora), an alkaloid of the nightshade family, for pain relief, and garlic for heart and circulatory disorders. (This information comes from the Ebers Papyrus about 3,500 years ago, along with hundreds of other remedies.) Opium for its sedative and headache-curing properties.
Western medicine can be
traced back to the Greek physician, Hippocrates (470-377 BCE), who was
greatly influenced by both
Theophrastus, in the 4th century BCE, a student of Aristotle, wrote De Historia Plantarum, describing the medicinal properties of 455 plants.
Around the 1st century CE, Western medicine was strongly influenced by the works of Dioscorides, a military physician who compiled accounts of over 600 species of plants with medicinal value in his De Materia Medica. It included both descriptions and illustrations of plants, along with preparations, uses, and side effects of the drugs.
These works represent a transformation of medicine based on supernaturalism and magic, to scientific medicine - the examination of natural phenomena thru critical application of rational principles.
Some of the herbal remedies used by the Greeks and Romans were effective treatments that have become incorporated into modern medicine.
E.g. - willow bark tea - the precursor to aspirin, was used to treat gout and other ailments.
(Gout - excess of uric acid in blood, and deposit of uric acid salts in tissues, especially in joints of hands and feet causing swelling and pain).
Early Renaissance (15th century) saw an increased interest in herbals (identification of medically useful plants), most of which were based on the work of Dioscorides, and included among them:
John Gerard’s The Herball, or Generall Historie of Plantes (1597), comprised of 1392 pages, 2,200 woodcut images of medicinal plants.
Nicholas Culpepper’s The Complete Herbal which, in addition to focusing on medicinal uses of plants, revived interest and influence of the Doctrine of Signatures - which held that the medical use of plants could be ascertained by recognizing distinct “signatures” visible on the plant that corresponding to human anatomy. Where some morphological feature of the plant indicates its utility. E.g. the red juice of bloodwort should be used to treat blood disorders; lobed appearance of liverworts suggest their use in treating liver complaints.
In the early 16th century, the Swiss, Philippus Theophrastus Bombast von Hohenheim, later known as Paracelsus a man who was to impart a great influence over modern medicine, thought that high colleges “produced so many high asses…To truly learn medicine a doctor must seek out old wives, gypsies, sorcerers, wandering tribes, old robbers, and such outlaws and take lessons from them”. Knowledge needed by doctors, “lies in the mysteries of Nature,” not in secondhand learnings “borrowed from books.”
Paracelsus is remembered today because he argued that the medicinal value of plants came from the chemicals within them – the perspective that dominates modern science. The most desirable parts of plants are not the leaves, bark, stems, or roots – a plant works best if you extract or distill its essence on the form of tinctures.
His work was a major step towards the present-day pharmaceutical approach toward plants: isolate the pure form of plant constituents, particularly the active ingredient: homogenize, standardize, and measured (uniform and consistent).
Lived at time of Copernicus, whose proof that the earth revolves around the sun was one of the major steps toward what we now call modern science. The new philosophy relied on experimentation, not on citations from ancient authorities, as the source of truth. Everything became open to question: Posit a hypothesis, conduct experiments to determine its validity, confirm the experiments results by replicating them. Rejection of the mystical
It is logical to assume that the plants we use for medicines were first encountered in our quest for nourishment, and since then, we have used these chemicals for their beneficial properties.
The dichotomy between food and medicine may be taken for
granted in Western society, but the distinction is not so strong or apparent in
many other cultural traditions. (Of course, diet and nutrition may be part of
the healing process). Among the Hausa people of
The distinction between food, beverages, condiments, medicines, stimulants, psychoactive agents, and toxins (poisons) are not so clearcut.
To some extent the line between foods and medicine, beverages and medicine, beverages and food, herbs and spices and medicine, toxins and medicines is a blurred line.
1. The limes sea-faring men wd eat on long voyages to prevent against scurvy - were the limes food or medicine?
2. The coffee you drink in the morning for the caffeine to perk you up, get you alert - a beverage quenching your thirst or a medicine?
3. Some of the spices we put on foods for palatability also impart antimicrobial benefits or perhaps physiological cooling - the capsaicin in chili peppers, spice or medicine?
4. The gin and tonic a British colonial wd drink on the veranda of his tropical Indian home had enough quinine in the tonic to act as an antimalarial - a beverage or a medicine?
5. The morphine derived from the opium poppy, used in the synthesis of heroin, is also a major analgesic - a drug, toxin, or medicine?
The frothy beer drunk in
the Middle Ages, loaded with carbohydrates and
calories at a time when so much of the available water was tainted and food
unavailable - beverage or food? And beer was often used in ancient
Often the difference between a poison and a medicine is simply a matter of dosage and/or context. They are 2 sides of the same coin.
The use of plants
for arrow poisons is widespread around the world, especially prevalent in
2. Similarly, African vines in the genus Strophanthus were first used as arrow poisons, but are now known to western medicine as the source of oubaine, a cardiac glycoside with rapid effects in heart emergencies.
3. Traditional medicine systems recognize the relationship between poisons and medicinal plants. Poisonous plants in appropriate quantities can be part of medical preparations, and traditional herbal medicines, just like modern pharmaceuticals, can have toxic side effects.
4. Because of potential toxicity, the medical application of plants require a sophisticated understanding of a plant’s ecology. The concentration of a plant’s toxins may be environmentally-sensitive (like the HCN levels of cassava: hydrocyanic acid): Read from p.28 of Nature’s Medicine
1. they must be picked at the right time of season
2. the proper part of the plant must be used (different plant parts not only have differing concentrations of secondary compounds, but also different secondary compounds)
3. this refers to the natural variability on secondary compounds among plants of the same species or even parts of the same plant.
Active Principles in Plants
The medicinal value of plants is directly related to the vast array of chemical (bioactive) compounds that have most likely evolved as chemical defenses against predation or infection.
Terpenes – compounds made of carbon and hydrogen, responsible for the pungency of pines and firs, and are named for the turpentines that can be distilled from the resin of some of these conifers.
a. The antimalarial compounds found in neem trees (Azidirachta indica) are terpenes.
b. The tetrahydrocannabinol found in Cannabis is a terpene-based compound.
c. Paclitaxol (taxol), another complex terpene, was first found in the Pacific yew tree (Taxus brevifolia) during a screening of No. American plants by the National Cancer Institute. It prevents the spread of cancerous cells by preventing microtubules from separating chromosomes; it halts uncontrolled growth associated with malignancies.
Alkaloids – scientists in the 19th century began to search for alkaloidal drugs by making powder of plant parts, mixing it with water, alcohol, or dilute acids. They then purified and filtered the mixture, extracting the alkaloids with a solvent. They scoured old herbals, followed leads by physicians, apothecaries, herbalists in identifying and collecting plants, which they subjected to their extraction processes in order to isolate compounds with medicinal value.
a. caffeine, theobromine, cocaine, morphine, codeine,theophylline, strychnine, mescaline,etc.
b. Discovery of alkaloids is a colorful chapter in the history of chemistry that began with the basic pharmaceutical question: why was some opium more potent than others?
i. Opium was known to be a mixture of plant chemicals, and the only way to standardize doses for pain relief would require separating the components of opium.
ii. Friedrich Serturner (1783-1841) extracted crystals of a bitter alkaline substance, which he masked with sugar syrup and fed to mice, cats, and dogs.
iii. Using trial and error, he worked out doses that would put these animals to sleep but not cause coma or death.
iv. A few years later, he dosed himself with the compound to relieve a toothache, and it worked so well he began to use humans as “guinea pigs” in experiments with his purified compound.
c. The tropane alkaloids (of the tomato family) gave us:
v. Scopalomine: used as a “truth serum”, and to alleviate pain during child birth.
vi. Atropine: used in eye examinations because it keeps the iris of the eye open by blocking the sphincter muscles.
Glycosides - so named because a sugar (glucose) molecule (glyco-) is attached to the active component of the molecule. 3 major types of glycosides:
1. cyanogenic glycoside –
a. releases cyanide upon breakdown (HCN) - recall cassava with its cyanogenic glycosides.
b. Amygdalin is a cyanogenic glycoside found in the seeds and pits of almonds, peaches, plums, apples, and apricots.
c. The pits of apricots are rich in amygdalin and are ground up in a preparation of laetrile, a controversial cancer treatment.
d. (Theoretically, laetrile releases HCN only in the presence of tumor cells and thus selectively destroys them by disrupting metabolic activity of mitochondria.)
2. cardioactive glycosides –
a. Has its effects on the contraction of the heart muscle and, in proper doses, can be used to treat certain forms of heart failure.
b. Digitalis is one of the best known medicinal cardioactive glycosides.
c. Some of the deadliest plants, Nerium (oleander) and milkweed, however, contains toxic levels of the cardioactive glycoside.
3. Saponins –
a. often highly toxic (severe gastric irritation and hemolytic anemia),
b. but diosgenin from yams (Dioscorea spp.) is used as a precursor for synthesis of hormones such as progesterone (one of the female sex hormones and an ingredient in birth control pills) and cortisone
Foxglove (Digitalis purpurea)
Today, in the
2. Knowledge of the foxglove plant goes back to at least to the latter part of the 16th century when John Gerard included it in his Herbal claiming that it cleared up the liver and spleen. But Gerard’s claim for the effects of foxglove on internal organs wasn’t examined until 1775, nearly 200 years later.
William Withering was an
English country doctor who, knowing the local flora of the area,
must have been somewhat familiar with foxglove. In 1775, his interest in it as
a medicinal herb was aroused when he was asked about the cure for dropsy, and
was told that an old woman from
a. Dropsy is a condition characterized by severe bloating due to fluid accumulation in the lungs, abdomen, and extremities. The fluid retention is due to congestive heart failure, a failure of the heart to pump sufficiently. (This was not properly understood in Withering’s day by him or other physicians).
The remedy the
c. He began treating dropsy patients with digitalis tea prepared from ground leaves, and at first admitted to giving it in doses too large.
d. Over the next 10 years he conducted careful experiments with powdered digitalis leaves to determine dosage, preparation, and effectiveness in treating dropsy.
e. From a practical standpoint, Withering realized that the therapeutic dose of digitalis is alarmingly close to the toxic overdose, which is characterized by delirium, disorientation, and death.
f. He believed that foxglove primarily acted as a diuretic in relieving dropsy. Altho, he did note that digitalis had a “power” over the heart, he never positively made the connection between dropsy and heart failure.
g. Digitalis is a cardioactive glycoside which slows the heart rate while increasing the strength of each heart beat so that more blood is pumped with each contraction. The improved circulation decreased the edema in the lungs and extremities, and increased kidney output.
1. By promoting a regular heartbeat, digitalis causes more blood to reach the kidneys, where excess fluids are removed rather than accumulate in body cavities or soft tissue.
Two points about Withering and foxglove:
1. The therapeutic index of foxglove treatment is relatively low. While the digitalis glycosides are an effective treatment for congestive heart failure, there is a fine line between a therapeutic and a toxic dose of digitalis. Even patients under a doctor’s care can experience toxic side effects, and must be carefully monitored for the correct dosages.
a. The toxicity of medicines and poisons is commonly expressed as the LD-50 - the lethal dose of 50%. Usually measured in grams/kilograms of body weight, it signifies the amount of a substance necessary to result in death for 50% of the unfortunate subjects.
b. The relative safety or danger of a drug is denoted by its therapeutic index, its margin of safety. This is the ratio of the drug’s LD-50 to its effective dose, the dose necessary to produce the substance’s desired effects. LD-50: effective dose = therapeutic index.
c. The larger the therapeutic index, the safer the drug. A high therapeutic index implies a high LD-50 (meaning it takes a lot of a specific drug before it results in the mortality of 50% of its subjects) and/or a low effective dose (meaning it takes very little of a particular drug to produce its desired effects). The larger the therapeutic index, the greater the discrepancy between the lethal dose and the effective dose. Eg. the therapeutic index of alcohol is ca. 5. That is, 5 times the amount needed to get you high (tipsy, etc.) cd kill you. As recreational drugs go, it’s very dangerous. The therapeutic index for digitalis is considerably less.
1. The difficulty Withering had in standardizing the dosages from ground leaves. Withering wrote: “These I had found to vary much as to dose, at different seasons of the year; but I expected, if gathered always in one condition, that is, when it was flowering late, and carefully dried, that the dose might be ascertained as exactly as that of any other medicine..” Here he is aware of the variability of the plant’s concentration of the active principle. The concentration of glycosides may be effected by its environment, by its phenology, by its plant part, etc. Withering attempts to standardize his collections of foxglove leaves in order to standardize the dosage and effects.
Snakeroot (Rauwolfia serpintina) Apocynaceae. - the genus honors the 16th century physician/botanist, Leonhard Rauwolf. Specific epithet describes snakelike appearance of its root.
Within sight of
2. Legend has it that mongooses wd feed on the plant before engaging in combat with cobras. Copying the reputed activity of the mongoose, local people found the shrub cd serve as a potent antidote to snake bite.
The plant was sent to
the herbarium in
In the 1930s
5. The sedative effects of reserpine (it depresses the central nervous system) made it valuable as one of the first tranquilizers prescribed for treatment of schizophrenia.
6. It also reduced the patient’s blood pressure, and today is used to treat hypertension (high blood pressure). The alkaloids act on the nervous system by blocking neurotransmitters. This results in the dilation (relaxation) of blood vessels, causing blood pressure to drop.
the belief in the Doctrine of Signatures. Because of the long coiled
roots that resemble a snake, healers believed the root cd
be used for treating snakebites. And for over 4,000 yrs, Hindu healers in
8. How to characterize the discovery of reserpine? Does discovery of this important drug rest on “solid” science, such as structural chemistry and pharmacology, or is it attributable to folklore and legend? Laboratory scientists hail the invention of reserpine as serendipitous, but 1 fact is inescapable - a plant used by indigenous people eventually became the source of one of the world’s most important pharmaceuticals.
1. Quinine is an odorless, white powder with an extraordinarily bitter taste.
2. It is useful against malaria, the disease caused by the mosquito-borne transmission of the protozoan Plasmodium.
Quinine is valued as a
flavoring agent as well as a medicine. Most quinine imported into the
4. Malaria had plague populations throughout the world for millennia; its characteristics are recurring onset of fever and chills, anemia, an enlarged spleen due tit he destruction of red blood cells. Untreated, malaria can result in cerebral malaria, characterized by convulsions, seizures, and coma, and can lead to death.
5. Disease is initiated thru the bite of the female Anopheles mosquito that had previously fed on the blood of an infected person. The mosquito carries a stage of the parasite in its salivary glands and injects the parasite into the bloodstream with its bite. The parasite multiplies in the liver and eventually releases merozoites (asexual stage in the life cycle of the parasite) inot the bloodstream. The merozoites invade red blood cells and multiply; after a while red blood cells rupture, releasing a new generation of merozoites that infect other red blood cells. The cycle is synchronous with simultaneous rupture of red blood cells and release of merozoites and toxins, which cause the periodic fever and chills.
The bark of the fever
bark tree was the first effective treatment for malaria (= bad air in
Italian; the belief that bad air near the swamps caused the disease). Incas
called the tree quina-quina (meaning bark of
barks). It is native to the eastern flanks of the
The genus of the tree is
Cinchona, named by Linnaeus, in honor
of a countess (wife of the viceroy of
8. In 1820, two French scientists isolated the alkaloid quinine from the bark; altho the alkaloid was discovered no one cd yet synthesize it. Quinine producers still relied on massive supplies of bark collected from wild Cinchona trees.
Quinine acts on the merozoite stage, killing the parasite in the bloodstream.
It’s also effective as a prophylactic, preventing the initial infection of red
blood cells in travelers visiting malaria-infested regions. (This bought about
the use of tonic water by the British in
10. After WWII, synthetic antimalarial drugs such as Maloprim and Fansidar reduced the need for quinine. Today the most widely used drug in the treatment of malaria is chloroquine, less toxic and more effective than quinine. It also lacks some of the side effects characteristic of quinine use: tinnitus (finging in the ears)blurred vision, depression , and miscarriages.
have been investigating properties of the temperate weed Artemisia annua, wormwood. Long used in
1. The most widely used synthetic drug (Americans consume about 80 million tablets a year), has a botanical origin.
2. The bark of willow trees (Salix spp.) has long been known as an effective treatment for reducing fever and relieving pain.
3. The ancient Greeks used an infusion of the bark from white willow (S.alba) to treat gout, rheumatism, pain, and fever. Many Native American tribes independently discovered the healing powers of the willow bark. The Chickasaw Indians prepared root infusions of Salix alba to relieve headaches.
4. In 1828, salicin was isolated from the willow bark. Salicin is an glycoside of salicylic acid (salicylates occur widely in species of Salix as well as Spirea ulmaria, poplars (Populus), and wintergreen (Gaultheria procumbens).
5. In 1898, while looking for a compound that caused less gastric distress, Felix Hoffman, a chemist with Bayer Co., came across acetylsalicylic acid in the chemical literature. This new compound was called aspirin: “a” from acetylsalicylic acid, and “spirin” from Spirea, the plant from which salicylic acid was first isolated. Salicin and salicylic acid refer to its Salix origin.
6. Aspirin is valued for:
a. anti inflammatory properties
b. antipyretic (fever-reducing)
c. analgesic (pain-relieving)
d. prevention of heart attacks - administration of aspirin following a heart attack or stroke reduces the risk of a second heart attack or stroke. It also statistically reduces the likelihood of an initial heart attack in men, and studies show it probably also has prophylactic effects with women as well.
e. aspirin suppresses the aggregation of blood platelets, a necessary step in the formation of blood clots that can block blood vessels and lead to heart attacks and strokes.
f. Aspirin suppresses prostaglandins (grp of local hormones): an overproduction of prostaglandins leads to headaches, fever, menstrual cramps, blood clots, inflammation, and other complaints. Prostaglandins also prevent the overproduction of acid in the stomach, and promotes the secretion of mucus that blocks self-digestion of the stomach lining. So, coupled with relief from headaches, menstrual cramps, fevers, etc, comes irritation of the stomach lining with the administration of aspirin.
Aloe vera (Liliaceae)
1. A folk remedy familiar to most people here is the administration of the cut leaf of Aloe vera to a burn or wound.
Aloes are succulent
perennials, native to
3. The cut, succulent leaves yield a thick, mucilaginous sap that can be soothing when applied to injured skin. The sap is comprised of a number of glycosides and chrysophanic acid (healing effect on the skin), and studies have shown that the aloe sap promotes faster healing with less scarring by stimulating cell growth and inhibiting bacterial and fungal infection in injuries ranging from deep dermal burns to radiation burns. Contents in the sap also inhibit itching, pain, and inflammation.
4. The aloe sap may also be used as a purgative for the relief of constipation: the anthraquinoines (glycosides) irritate the gastrointestinal tract, resulting in purgative action.
5. It has traditionally been used as a treatment for diabetes, and now shows some promise in lowering blood glucose levels among a small group of noninsulin-dependent diabetics.
6. Its moisturizing effects have been capitalized upon by a number of companies that employ the sap in a variety of skin creams, shampoos, conditioners, bath oils, etc.
1. An alkaloid produced by members of the gymnosperm Ephedra spp. , Mormon or Indian tea.
2. Various species (Asian spp.) have a long history of use in herbal medicine as a decongestant for asthma, bronchitis, and other respitory ailments.
4. The alkaloid was first identified in 1887, and ephedrine was first used in modern prescription drugs in the 1920s.
5. As a decongestant, ephedrine relaxes bronchial muscles.
6. Several spp. of Ephedra were used to treat venereal disease: E. antisyphilitica was used with other Ephedras in combination called “clapweed” or “whorehouse tea”. The Hopi and Navajo used the plant to treat venereal disease.
7. It also stimulates the central nervous system, which is similar in action to adrenaline; it increases the heart rate and blood pressure and also increases blood flow to the heart and brain. (Today, pseudoephedrine, another Ephedra alkaloid, is preferred as the active ingredient in decongestants because its stimulating properties aren’t as great)
8. Ephedra products have been used as substitutes to the street drug “herbal ecstasy” because of its amphetamine-like effects. It is also found in over-the-counter weight-control supplements, and herbal energy boosters.
9. North American species of Ephedra are lacking in the ephedrine alkaloid, but has other pharmacologically-active compounds that protect plants from pathogens and stem and seed-feeding insects. The high levels of kynurenates in the stems of some desert species may screen photosynthetic tissue from radiation damage.
Altho Western medicine strayed away from herbalism, 75-90% of the rural populations in the rest of
the world still rely on herbal medicine as their only health care. This long
tradition of herbal medicine persists today throughout
Relatively recent discoveries of plants that have some remedial effects to modern-day illnesses have reawakened an interest in herbal medicine or plant-derived drugs in Western medical practice.
1. A vinca, Rosy periwinkle, Catharanthus roseus (Apocynaceae: Dogbane),
a. perennial herb native to the tropics,
b. contains alkaloids vincristine and vinblastin which are being used in treatment of pediatric leukemia and Hodgkin’s disease. (The plant had been used traditionally by healers for the treatment of diabetes).
2. The Pacific yew tree, Taxus brevifolia,
a. contains the alkaloid, taxol, which has anti-tumor properties, and appears especially promising in treatment of ovarian and breast cancer.
b. Taxol is from the bark of
the mature, Pacific yew tree, a slow-growing conifer of the old-growth forest
c. These were once considered “trash trees” by the timber industry, and were routinely burned after clear-cutting. 90% of the original yew population disappeared before the medicinal value of the tree was realized.
d. (Concern for the ecology of old growth forests have led to the investigation of taxol-producing tissue cultures of the bark cells. Taxol has recently been synthesized in the laboratory).
a. Used in the treatment of depression. In past, used in healing wounds and relieving gastric upsets.
b. Cited in the works of Pliny, Hippocrates, Dioscorides
4. Ginkgo biloba
a. Staple of Chinese medicine for 4,000 years. A tea from the leaves was used to treat asthma and bronchitis.
b. Recent studies have demonstrated that a daily regimen of ginkgo extracts results in stabilization or improvement of brain function in elderly who suffer from mild dementia.
c. Concentration and long-term memory are enhanced. It may halt the progression (or degeneration) of Alzheimer’s disease.
d. Ginkgo leaf extracts has its primary effects on the circulatory system. The aggregation of platelets (blood clotting factors) is inhibited. Increased blood flow to the brain delivers more oxygen and nutrients, and arrests the death of nerve cells due to vascular impairment.
Physicians are no longer botanists, and they prescribe plant chemicals as medicines based on their efficacy, regardless of their role in nature. An appreciation of ecosystems, natural selection, and survival is not necessary to practice medicine in developed countries. We should nevertheless not forget the plants invest energy and resources in producing chemicals as strategies to sustain their lives; for millions of years, natural selection has favored the chemically potent plants that survive when attacked by hungry dinosaurs, caterpillars and moles. The array of plant compounds available for medicinal uses reflects the challenges and travails of life on earth for green photosynthesizing survivors.