Medicinal Plants

Ancient archaeological records of medicinal plants

3500 BCE - India had an extensive pharmacopoeia. Much of that knowledge is still used as part of the Ayurveda medical system

2250 BCE – Egypt and Babylon were trading medicinal plants

900 BCE - Archaeological records demonstrate the use of medicinal and psychoactive plants in the New World

330 BCE - One of the Theophrastus’s students, Alexander the Great, sent medicinal plants from Asia back to Greece for cultivation

2000 YA - The first written Chinese records although use is probably as ancient as India’s

Use of Medicinal Plants

• Use of medicinal plants developed from informal experimentation and based on a general familiarity with medicinal plants. This knowledge was amassed via experimentation over many generations and was handed down orally from person to person – often woman to woman in traditional cultures.

Theophrastus370-285 BCE

History of Herbals• Dioscorides, in the 1st Century AD, was a Greek physician

who described the medicinal properties of plants - he described the use of 500 species of plants in his book De Materia Medica

• The first herbal written in the Anglo-Saxon world was an 11th Century book known as the Herbarium of Apuleius Platonicus

• The first herbal to break from Dioscorides and print descriptions of local flora, with accurate drawings of the plants was by Leonhart Fuchs, his extremely well illustrated herbal De Historia Stirpium was published in 1543

Page from “Vienna Dioscorides”Arabic – 6th Century

Page from Arabic edition of Dioscorides herbal 1334

Title page from Fuchs herbal –1543

Page from Fuchs Herbal 1543

Papaver or Poppy

More from Fuchs Herbal 1543

Nicotiana - Tobacco

English Herbals

• The earliest printed English herbal was anonymous volume from 1525 published by Richard Banckes

• In 1526, Peter Treversi published an English translation of a French herbal

• In 1538, William Turner published an herbal entitled Libelluls de re Herbaria Novus

• In 1551, Henry F. Lyte published an English translation of Rembert Dodoen’s herbal Stirpium Historiae Pemptades Sex which was valued because of its all inclusive treatment of many plants and excellent plates illustrating flowers

Best English Herbals• In 1597, John Gerard published his outstanding book The

Herball, Or Generall Historie of Plantes - it is a huge volume of 1392 pages and 2200 woodcut illustrations of plants - it was widely used by physicians and became widely quoted and referenced - the book has remained in print for 400 years

• The last major herbal published in English was John Ray’s herbal, published in 1688 - it is also a major taxonomic work and Ray was the first person to divide the flowering plants into two main groups - the dicots and monocots

Cover of Gerard’sHerbal – 1597

Page from Gerard’s Herbal - 1597

Title Page of John Ray’s Herbal - 1688

Page from John Ray’s Herbal - 1688

Ginseng root – Panax pseudoginseng

Foxglove –Digitalis purpurea

• Foxglove may be useful as a way to cure people of “grosse and slimie flegme and naughtie humors” – from Gerard’s Herbal - 1597

William Withering- holding a foxglove

Withering’s work on Foxglove• Began experiments with foxglove in 1775 -

Withering had heard about an old family cure for dropsy

• Reported his findings in a paper published in 1785, “An Account of the Foxglove and Some of its Medical Uses”

• Powdered foxglove leaf is still prescribed in tablets or capsules to treat congestive heart failure

• The somewhat crude powdered drug is called Digitalis after the plant

• Foxglove produces more than 30 different cardiac glycosides - two in particular - Digoxin and Digitoxin are produced from foxglove and prescribed to heart patients around the world today

Foxglove - Digitalis purpurea

Willow Bark – inspiration for Aspirin

Urgent need to study medicinal plants

The utility of plants in current therapy

There has been a rush to develop synthetic medicines based on plant medicines, but often the synthetic medicines don’t work as well as the original plant medicines.

For example – quinine and malaria

Efficacy of Quinine

• Quinine is traditional and effective preventative of malaria

• Synthetic preventatives such as chloroquine, maloprim, and fansidar have largely replaced the use of quinine

• Many strains of Plasmodium have developed resistances to the synthetics and the synthetics are more toxic. It is recommended that people do not take fansidar for more than 3 months due to potential liver damage.

Malaria Cycle

Anopheles freeborni mosquito – intermediate host and vector for Plasmodium sp.

Historical distribution of Malaria

Red areas show countries with malaria today

One of the sources of Quinine – Cinchona succirubra

Cinchona pubescens

Timeline of Quinine Use

• 1633, a Jesuit priest named Father Calancha described how to use quinine bark to cure fevers

• 1645 Father Bartolome Tafur took some bark to Rome and many of the clergy used it

• Cardinal John de Lugo wrote a pamphlet to be distributed with the bark - use of the bark became so widespread that in the papal conclave of 1655 no one died of malaria

• 1654 – English aware of use of quinine bark• 1735, a French botanist named Joseph de Jussieu

journeyed to South America and found and described the tree that is the source of the bark - he sent samples to Sweden where in 1739, Carl Linneaus named the tree genus Cinchona

Timeline of Quinine Use• 20 to 40 species of Cinchona - the species are very

hard to tell apart and the species will hybridize, so the exact number of species is unknown – mostly understorey trees

• 1820 the French chemists Joseph Pelletier and Joseph Caventou isolated the alkaloid quinine from the bark and identified it was the active ingredient in Peruvian bark

• 1861, an Australian named Charles Ledger obtained seeds from an Aymara Indian named Manuel Incra

• by 1930, the Dutch orchards in Java produced 22 million pounds of quinine, 97% of the world’s market

Charles Ledger – 1818-1906

Chemical structure of quinine

Properties of Quinine

• Quinine itself is an odorless white powder with an extremely bitter taste

• It can be used to treat cardiac arrhythmias as well as malaria - it is also used as a flavoring agent

• Quinine prevents malaria by suppressing reproduction of the Plasmodium protozoan and also helps prevent some of the fevers and pain associated with malaria

Quinine fluoresces under UV light

Raymond Fosberg in the field in 1948

Cinchona bark drying in the sun in Ecuador, 1944

Arrow Poisons

Documented use of arrow poisons around the world

Monkshood – Aconitum ferox – source of Acontine

Monkshood – Aconitum ferox in the wild

Uses of Aconitum

• In Europe the plant has been used as a liniment or tincture in the treatment of neuralgia, sciatica, and rheumatism, and taken internally to alleviate fevers.

• In India and China the plant is still used in treatment. In the raw state, tubers are applied to the skin as a surface anaesthetic and to treat lumbar and leg pains, neuralgia and rheumatoid arthritis. After much processing it is used for cardiotonic and diuretic properties.

• Acontine is an alkaloid derived from monkshood - used in heart medicines, common cough medicines, and used in fly control in Europe since 1240

First Ethnobotanical Chemical Isolation - Strychine

• 1805 – Leschenault describes the preparation of the Javanese dart poison Upas Tieute.

• 1809 – Magendie and Delile publish accounts of experiments on mechanism of action of the poison.

• 1819 – Pelletier and Caventou isolate strychine from other sources. Magendie uses strychine in clinical medicine.

• 1824 – Pelletier and Caventou isolate strychine from upas tieute

• 1963 – total synthesis of strychine by Woodward et al.

Strychnos nux-vomica - source of Strychine

Strychnos nux-vomica leaves and seeds

Strychnos

• Interestingly there are about 200 species in the genus Strychnos but only 6 actually contain strychine – in particular S. nux-vomica, S. ignatii (St. Ignatius’ bean), S. colubrina (snake wood) and S. guianensis. Strychine is commonly used in rat poison. It has been used to stimulate circulation, but that cannot be recommended because it frequently poisons the patient.

Curares

Calabash curare from Strychnos guianensis – carried in gourd

Crescentia cujete – source of calabash gourd

Tube Curares – made from members of Chondrodendron and other moonseeds -

Menispermaceae

Chondrodendron tomentosum leaves and vine

Tube and Calabash Curares

• The bamboo tube curare yielded tubocurarine and the calabash gourd curare yielded toxiferine - both are useful as an anaesthetic in open-heart surgery - these are muscle relaxants which kill by relaxing muscles which allow breathing

Bark being scraped to start preparation of curare

Liquid dripped through shavings to extract Curare

Curare added to arrow/dart tips

Waorani man

Toxicities of several arrow poisons

Anti-tumor medicines from Arrow Poisons?

• There is a possibility that plants producing arrow poisons may also have value in producing anti-tumor medicines. Spjut and Perdue (1976) surveyed 76 species from 63 genera in 29 families and found that 46 of the species had been screened for anti-tumor activity. Of these 52% of the species and 75% of the genera had been found to have anti-tumor activity. This high anti-tumor activity probably comes from the fact that arrow poison plants almost all produce cardenolide glycosides that are cytotoxic (kill cells).

Herbal Medicines Today

• Though many modern cultures make extensive use of herbal remedies, most notably in India and China, much of Western medicine has moved away from herbal medicines. In Great Britain there is still a tradition of homeopathic doctors and herbal Culpeper Shops. Homeopathy is based on using minute quantities of substances that in massive doses produce effects similar to those of the disease being treated.

Nicholas Culpeper1616-1654

Culpeper’s Influence on Homeopathy

Grave’s patent medicine – a Laudanum product

Medicines from Plants

• About 25% of the prescription drugs used in the western world have active ingredients that are derived from plants – often the only way to acquire these drugs is through growing and harvesting the plants because synthetic substitutes are not as effective.

• 89 plant derived drugs that are currently used in western medicine as prescription medicines were discovered by studying folk knowledge of the plant’s properties

Strychnos toxifera – source of D-tubocurarine

Mexican yam – Dioscorea villosa Source of cortisone

Indian snakeroot – Rauwolfia serpentina –Source of reserpine

Madagascar periwinkle Catharanthus roseus –Source of vincristine

White Hellebore – Veratrum album Source of hypotensive alkaloids

Medicinal Plants in the Amazonian Basin

• 3 million square miles in size, supports the world’s largest rainforest with an estimated 80,000 species of plants, about 15% of the world’s species

• The northwest section of the Colombian Amazon is home to 70,000 Indians in 50 ethnic groups that speak many languages from 12 linguistic families. They have been recorded to use medicines made from almost 1600 plants from 596 genera in 145 families

Cannabis sativa and C. indica

Cannabis sativa and C. indica

Cannabis sativa x indica hybrid

High tech Cannabis growingin the Netherlands

UK Police Bust of High-Tech Growth

World Cannabis Laws - 2011