Medicinal Plants

Lecture 16: Medicinal Plants

Overview

• Outlines are due by midnight.
• Quiz on Wednesday, April 2.

History of Tea (Camellia sinensis)

• Origin: China
• Evidence of cultivation around 3000 BC.
• Early use as medicine, later as a beverage, around 2737 BC.
• Monks and priests used it to stay awake during meditation, similar to coffee.
• Around 750 BC, evidence of use in India and in the 8th Century to Japan.
• 1500s: Portuguese brought tea to Europe.
• 16th Century: English introduced tea during King Charles II and Queen Catherine's reign.
• Afternoon tea became a British mainstay in the 19th century.
• December 6, 1773: Boston Tea Party, protest against British Parliament's Tea Act (taxes) of 1773.
• Today: Cultivated across the world, mostly in tropical and subtropical regions.
• Grown in over 52 countries, an important cash crop in many developing countries (> 245 billion).
• China and India are the largest tea-producing countries.

Types of Tea

• Derived from fresh tea leaves of Camellia sinensis.
• White Tea: Steaming, then drying.
• Green Tea: Steaming or pan-frying, then drying.
• Oolong Tea: Withering, shaking, partial fermentation, rolling, pan-frying, drying.
• Black Tea: Withering, shaking, full fermentation, rolling, drying.

Herbal Medicine

• Used since pre-history.
• 1550 B.C.: Ebers papyrus (Egypt) with 850 plant medicines (e.g., garlic, cannabis, aloe).
• 2000-5000 B.C.: Sumerian use of 100s of medical plants.
• First recorded use of Heroine Poppy.
• Pre-2000 B.C.: Mesopotamian clay tablets with 100s of medicinal plants.
• 1552 A.D.: Badianus Manuscript, Aztec medicinal herbs written by Spaniard Martin de la Cruz, based on centuries-long oral history.
• Knowledge likely lost due to Spanish Conquistadors.
• 1600: Pun-tsao, Chinese pharmacopoeia (>2000 B.C.) attributed to Emperor Shen-nung, with 1,000s of herbal cures.

Medicine in Early Western Civilization

• Hippocrates (460-377 B.C.): Greek physician, Father of Medicine.
• Primary treatment: herbal remedies and physical rest.
• Dioscorides (~64 A.D.): Greek physician in the Roman army, collected plants during military travels.
• Publication: Materia Medica (herbal).
• > 600 species and their medicinal uses.
• Primary source for medicinal plants for 100s of years.
• Dioscoreaceae (yam family).

Pre-Renaissance Botany (ca. 1000-1500 AD)

• Three critical areas of study:
  • Natural history (less critical)
  • Religious significance
  • Medicinal uses
• Doctrine of Signatures

Doctrine of Signatures

• Belief that God created everything with a “signature” indicating its use to people.
• Applied to medical uses of plants.
• Led to the age of “Herbals” (1400s – 1600s).
• Examples:
  • Hepatica (liverleaf).
  • Liverwort = relieve liver trouble.
  • Snakeroot = antidote for snake venom.
  • Adder’s tongue = cure for wounds and inflammation from snakebite.
  • Lungwort = cure for pulmonary diseases.
  • Bloodroot = cure blood disorders; induce vomiting; laxative.
  • Toothwort = relieve toothache.
  • Gravelwort = dissolve stones in the urinary tract.
  • Wormwood = expel intestinal parasites.
  • Pilewort = cure hemorrhoids.
  • Ginseng = "man essence," used as a general human panacea.
  • Mandrake = promote sexual passion in females.
  • Black-eye root = remove bruise discoloration.
  • Maidenhair fern = cure for baldness.

Mandragora officinarum (Solanaceae)

• Also known as Mandrake.
• Named for perceived resemblance to the human form – thus can alter human action.
• Western legend: The plant screamed when pulled by the roots from the ground.
• Dogs were employed for the task due to the noise's deafening effect on humans.
• Used in witchcraft and sorcery during the Middle Ages in witches' brews to induce hallucinogenic states for communing with the supernatural.

Modern Age

• 1775: Dr. William Withering – Foxglove extracts.
• 1900s: Half of drugs in U.S. Pharmacopeia still derived directly from plants.
• 1900s: Advent of “scientific medicine”.
• 2000s: 25% of prescription drugs of plant origin (most chemically synthesized from plant origins).
  *Foxglove - digitalin -Digitalis purpurea Heart Disease,
• 2000s: Alternative medicine; concern for biodiversity.
• CAM Natural Products Research NIH Funded.
• https://nccih.nih.gov/about/strategic-plans/2016

Plant-Derived Medicines

• Major Classes of Secondary Compounds from Plants Used in Medicine:
  1. Glycosides
     1. Cyanogenic glycosides (release cyanide)
     2. Cardioactive glycosides (steroids)
     3. Saponins (steroids)
  2. Alkaloids
  3. Terpenes

What is ‘Known’ Medicinal Value?

• Specific chemical extract has been identified.
• The extract is recognized as being the active ingredient; its specific effect on the body is known.
• Clinical tests have been performed.
• Statistically significant results.

Leaf Extracts

• Digitalin (glycoside).
• Digitalis purpurea - Plantaginaceae.
• First discovered as part of a cure for dropsy in the 1700s (originally tonic of 20+ herbs).
• Dropsy caused by congestive heart failure leads to bloating due to fluid accumulation in lungs, abdomen, extremities.
• Foxglove leaves contain over 30 glycosides (digoxin & digitoxin) medicinally significant for digitalin.
• Slows heart rate while increasing the power of each beat.
• Dosage is very important!

Dioscorea – Glycosides (Steroids)

• Tuberous.
• Wild Yam – convenient source for steroidal saponins, which can be converted into synthetic hormones & for use in contraceptives.
• George Rosenkranz developed in Mexico (1945) after being rejected by pharmaceutical companies in the USA.
• Diosgenin (glycoside) – progesterone and cortisone synthesized from this plant.
• Cheap way to make these steroids widely available.
• Also a source of starting material for the “pill”.

Salix spp. (Salicaceae) - Precursor to Aspirin

• Used leaves and bark.
• Hippocrates (Greece) – used Salix alba (white-willow) leaf or bark-tea to treat pain (as well as gout, rheumatism, fever).
• Native Americans independently discovered a similar purpose for Salix.
• 1800s: French & German chemists isolated salicin (glycoside of salicylic acid) from willow bark.
• Salicilates were also identified in other plants: meadowsweet (Spirea ulmaria - Rosaceae) and wintergreen (Gaultheria procumbens - Ericaceae) methyl-salicilate.

Aspirin Synthesis

• 1897 – Felix Hoffman of Bayer Co. (Germany) Chemist – synthesizes, names aspirin, (a[acetyl chloride] + Spirea) = (glycoside + terpene).
• Anti-inflammatory, anti-pyretic (fever reducing), analgesic (pain relieving).
• Suppression of prostaglandins which cause inflammation.
• Plant uses it as a defense response creating resistance to pathogens.

Malaria – Cinchona officinalis – Rubiaceae (Coffee Family)

• Use bark.
• Malaria – caused by protozoan, most widespread infectious disease in the world.
• Quinine – alkaloid attacks protozoan transmitted by mosquitoes.
• From the 1600s until recent times, the only known cure for the disease.

Cinchona

• “Bark of Peru”; ”yellow bark”; “Jesuit Bark”.
• About 40 species, but only one has a high quantity of quinine.
• The Peruvian government would not allow the export of seeds.
• During WWII, chloroquine (a synthetic – was toted as a potential miracle for Covid-19) is used – but resistant strains of Plasmodium have evolved.
• Native Grown “Stolen” by British, Dutch late 1800s

Artemisia annua – Asteraceae – Dulce Annie

• Use glandular trichomes.
• In development since the 1970s as a replacement for quinine for malaria.
• Origins in China, but now naturalized worldwide weed.
• Terpene – Artimisin.
• Effective and fewer side effects – but not a prophylactic (used after the fact).

Papaver somniferum – Opium Poppy – Alkaloids

• Use fruit.
• Chemically distinctive set of alkaloids – papaverines compounds are highly effective in the treatment of pain.
• Highly addictive forms (Morphine, Heroine).

Catharanthus roseus (Madagascar Vinka)

• Poster child for plant-derived medicines – used by contemporary herbal healers.
• Used by traditional healers in Madagascar as a cure for diabetes.
• Research shows no evidence of usefulness to that purpose.
• Vincristine (alkaloid) discovered in leaf extracts.
• Effective drugs vs. lymphomas (Hodgkin’s disease) – restricts mitosis.

New Drug Development

• Average to develop a new drug in the U.S. - 231 million/12 years.
• Many are not developed if patent protection is not available, or if the market is not assured.
• Regulations:
  • Germany - "reasonable certainty" of safety and effectiveness.
  • U.S. - "absolute proof".
• Some modern herbal preparations coming from Europe, sold as dietary supplements in the U.S.
• Examples: St. John's Wort, Echinacea, Gingko

Alternative Medicines

• Since the 1990s, there has been increasing use of alternative medicines.
• The FDA approves as dietary supplements.
• Sales now exceed 4 Billion annually in the USA.

Promising – Hypericumperforatum (St. John’s Wort)

• Depression – leaf extracts.
• In use by Hippocrates, Dioscorides for healing wounds and curing upset stomach.
• Research interested in its anti-depressant properties.
• Science shows it enhances serotonin in the brain, a mood-enhancing neurotransmitter.
• Used in Germany for over 25 years and is a leading treatment for moderate to minor depression.
• Dietary supplement - herbal remedy in USA – not approved as medicine.

Potentially Dangerous – Ginkgo biloba (Ginkgo)

• Alzheimers and dementia.
• Used by Chinese herbalists for over 4,000 years.
• Tea from leaves used to treat asthma and bronchitis.
• Mixed results in clinical trials for Alzheimer’s and dementia.
• Largest studies show no effect.
• Blood clotting inhibited, thus increases blood flow.
• Negative can be reactive with other blood thinners and cause severe bleeding.

Looking for New Drugs - General Parameters and Issues:

• 1 in 10,000 chemicals screened becomes a new drug product.
• Development of a new drug in the U.S. - 12 years/231 million (average).
• Many drugs/diseases are not pursued because of a lack of profitability.

Promising Research - Development of Phy 906 – Phytoceutica Herbal Medicine

• Based on Chinese Traditional Medicine first described 1800 years ago.
• Mixture of herbs: Scutellaria (skullcap), Glycyrrhiza (licorice), Ziziphus (jujube), Paeonia (peony).
• Application: treat nausea and pain associated with cancer chemotherapy regimes – heals intestinal lining.
• Initial results: not only effective against side effects but also appears to increase the efficacy of chemotherapy for certain cancers.

Issue in New Drug Development from New Plants: International Agreements

1. Discovery

   • -by pharmaceutical companies
   • -preceded by traditional healers

   Who discovered/Who should benefit financially?

2. Ownership

   • -seeds, genes, chemicals Cycle leading to poor country disadvantage
     • Gene poor country, has scientific expertise
     • Gene rich country, has genetic diversity but lacks science
     • development of chemical by gene poor country
     • now sell back to gene rich/economically poor country