Plants used to treat infectious disease - III

Plant Products as Antimicrobial Agents

Plant Products

• Secondary compounds produced by higher plants have a long history of use as antimicrobial agents

• Hundreds listed in literature and antimicrobial properties of many of these compounds have been tested

• Very few have made the transition from herbal remedies to mainstream drugs

Antimicrobials

• With the renewed interest in plant products it is possible that some of these compounds may make it into mainstream medical use

• Also the development of resistance to mainline antibiotics has also renewed interest in these plant products - with possibly novel means of attacking bacteria

Chaulmoogra Oil

• One of the few plant compounds used by physicians to treat infectious disease was chaulmoogra oil

• Chaulmoogra oil was formerly used for treatment of Hansen’s Disease (Leprosy)

Leprosy - Hansen’s Disease

• Chronic skin disease endemic to tropical and subtropical areas

• Caused by bacterium, Mycobacterium leprae (which is related to the bacterium which causes tuberculosis)

• Bacterium discovered by Gerhard Hansen - one of the first bacteria associated with a disease

• Transmitted: contact between susceptible people??• It has the potential to produce mutilation of

extremities and disfigurement of the face

Leprosy

• Effects skin and nerves• If untreated:

– lack of skin sensitivity to pain

– the skin takes on a porcelain-like whiteness

– the skin becomes mottled with color

– the eyebrows fall off, nasal ulcers develop, and there is facial deformity

– extremities may fall off.

Forms of leprosy

• Apparently two forms– Tuberculoid type may be limited to a few

nerves and skin area– Lepromatous type is disseminated throughout

the body

Leprosy - Hansen’s Disease

• Long history - leprosy was known in ancient times• Leviticus in Old Testament contains vivid

descriptions of what was many different skin conditions including leprosy

• For centuries leprosy was considered an incurable disease

• Lepers shunned or confined to colonies• Today, approx. 1 to 1.2 million afflicted with the

disease - US still has leper colony

Chaulmoogra Oil

• Mentioned in the Vedas (sacred Hindu texts) over 2000 years ago as helping in curing leprosy

• Oil reached Europe in the mid-nineteenth century, but source was still unknown

• Joseph Rock traveled Asia in 1920's, identified source of chaulmoogra as Hydnocarpus trees of India and surrounding countries

• Rock sent seeds to Hawaii, where Hydnocarpus plantations were started

• The only effective treatment for leprosy until sulfa drugs were first produced in 1946

Chaulmoogra Oil

• Possibility of slightly early use in Hawaii• Alice Ball (1892-1916) was a young black woman

who was the first woman to get master’s degree in science from University of Hawaii - 1915

• After graduation taught Chemistry at UH• Worked on chaulmoogra oil to treat leprosy• Unfortunately she became ill and died in 1916 (24

yrs old) - work was taken over by Arthur Dean who got credit for work with chaulmoogra oil

Chaulmoogra Oil

• Given by injection to patients with leprosy

• Was not a radical cure for leprosy

• Symptoms went away and bacteria disappeared from nasal secretions but relapse often occurred– Early cases were completely cured– More established cases had relapse

Herbal Remedies

Herbal Remedies

• Many herbal remedies on the mass market are known to have antimicrobial activity

• One example: berberine

• Several herbal remedies containing the alkaloid berberine show antimicrobial activity against a variety of bacteria, fungi, protozoans, worms, chlamydia, and viruses

• Extracts of these plants used in Ayurvedic and Chinese medicine for about 3000 years

Berberine containing herbals

Scientific Name Common Name Plant Part Used

Berberis aquifolium Oregon grape Rhizome, roots

Berberis aristata Tree turmeric Root

Berberis vulgaris Barberry Outer bark, root

Coptis chinensis Coptis,goldenthread

Rhizome

Hydrastis canadensis Goldenseal Rhizome, root

Berberine

• In one study, berberine had antimicrobial activity against gram-positive and gram-negative bacteria, fungi, and protozoa

• Much of the research focused on its use in cases of diarrhea, including that caused by Vibrio cholerae and Escherichia coli

• Berberine has been also shown to inhibit HIV-1 reverse transcriptase

Herbs and Spices

Herbs and spices

• Herbs are aromatic leaves or seeds from plants of temperate origin

• Spices are aromatic fruits, flowers, bark or other plant parts of tropical origin

• While herbs and spices are mainly associated with cooking, they are also used, as natural dyes, in perfume, cosmetics, and traditionally used in medicine

Essential Oils

• Value of herbs and spices due to essential oils - volatile substances that contribute to essence or aroma of certain plants

• Most commonly found in leaves, flowers, and fruits where they occur in specialized cells or glandular trichomes

• Chemically, essential oils are most commonly terpenes, but may be phenolics

Early history of spices

• Primitive people were attracted to aromas of these plants and found uses for them

• Ancient Egyptians used herbs and spices extensively in medicine, cooking, embalming, and as perfumes and incense.

• Many mentioned in Ebers Papyrus

Ebers Papyrus

• Anise, caraway, mustard, saffron and many others

• Other Egyptian records mention cinnamon and cassia, two spices native to Southeast Asia and China

• The use of these spices in Egypt is given as evidence that an active spice trade was already in existence

Ancient Greek trade

• During ancient Greek civilization, the spice trade was flourishing between the Mediterranean region and the Far East

• Spices such as the cinnamon and cassia as well as black pepper and ginger from India

• Arab merchants brought the spices by caravan from India, China, and Southeast Asia (Spice Islands in East Indies)

The Roman spice trade

• Spices were even more prominent in the Roman Empire

• After first century, Rome began trading directly with India by ship, breaking the centuries-old Arab monopoly

• When Rome fell in 476 A.D. the spice trade virtually disappeared

• Centuries elapsed before the spice trade actively resumed

Dark Ages

• Exotic spices from the East were rare

• Europeans had to rely on native temperate herbs and many valued for medicinal uses

• Merchant travelers kept a limited supply of spices from the Arab trading centers

• Crusades, beginning in 1095, increased the spices from the Near East

Marco Polo

• Venice and Genoa rose in 12th and 13th century• Venetian who influenced spice trade - Marco Polo• Traveled to the court of Kubla Khan in China in

1271 and spent 25 years in the Orient - saw its riches and wrote about it on his return

• Increased European desire for spices• Lured more and more travelers eastward• New overland routes were established and soon

explorers were searching for sea routes to the East

Henry the Navigator

• Prince Henry of Portugal wanted to break the Venetian-Muslim trade monopoly

• He established a school of navigation in 1418 to find a sea route to the Orient

• His efforts laid the ground work for the Age of Exploration

Age of Exploration

• Late in 15th century – Dias discovered the Cape of Good Hope at the

southern tip of Africa– Vasco da Gama reached the west coast of India – Columbus set off to discover a western route to

the Spice Islands - Led to introduction of capsicum peppers, vanilla, and allspice to Europe

Ferdinand Magellan

• Portuguese Ferdinand Magellan, also sailing for Spain, led the expedition that circumnavigated the globe (1519-1522) and discovered a western route to the Spice Islands

16th - 19th Centuries

• First Portuguese, then Dutch, and finally the British controlled the lucrative spice trade

• Country that controlled spices, controlled unbelievable wealth

• By the mid 19th century spice monopolies were over as various countries established plantations in their own colonies

Herbs and spices

• Over the past 30 years dozens of studies have focused on the antimicrobial properties of herbs and spices

• Most spices have antimicrobial properties

• Growing feeling that the enduring value of spices is actually due to these antimicrobial properties

• Paul Sherman from Cornell one of the leading proponents of this hypothesis

Why use spices?

• Obvious answer is that they impart pleasing tastes to foods:– Why do people find taste appealing?– Why are there preferences for certain spices in

cuisine of different regions?

Predictions based on spice use

• Sherman and his students developed antimicrobial hypothesis

• If spices kill microorganisms or inhibit their growth or production of toxins, then spice use would protect us from food borne illness and food poisoning

• To test the hypothesis, they developed critical predictions

Antimicrobial activity

• Prediction 1 - Spices used in cooking exhibit antimicrobial activity– Overwhelming evidence that most spices have

antimicrobial properties– Inhibition of bacterial especially important

because they are more common in food poisoning than fungi

Antimicrobial activity

• Of 30 spices for which information was available, all inhibited or killed at least 1/4 of bacterial species tested

• Half the spices inhibited or killed 3/4 of the bacteria

• Four most potent spices (garlic, onion, allspice and oregano) killed every bacterial species tested

Spice use in hotter countries

• Prediction 2: Use of spices should be greater in hot climates where unrefrigerated foods spoil quickly– Looked at spice use in traditional recipes and correlated

it with temperature

– Use of spices greater in hotter area

• Percent of recipes calling for at least one spice and the number of different spices were all greater in warmer countries - especially true for highly inhibitory spices (inhibited 75% of bacteria tested)

Spices use in hotter countries

• In 5 of the 6 hottest countries (India, Indonesia, Malyasia, Nigeria, and Thailand) every meat-based recipe called for at least one spice

• In the two coldest countries (Finland and Norway) more than 1/3 of the meat-based recipes did not call for any spices

Spice use in hotter countries

• In India, 25 spices used and the typical meat-based recipe called for 9 spices.

• In Norway, only 10 spices total used mean number was less than 2 per recipe

• Most powerful spices are most popular and they become increasingly popular as temperature gets hotter

Spices kill food-borne bacteria

• Prediction 3: Spices used in each country should be particularly effective against the local bacteria– Unfortunately no lists of native food-borne bact– Sherman et al looked at effectiveness of native

recipes in killing 30 common food-borne bact.– As annual temp increased, the estimated percent

of bacteria that would be inhibited also increased

More spices used with meats

• Prediction 4: Within a country meat recipes should be spicer than vegetable recipes– Unrefrigerated meats associated with more

food-borne disease outbreaks and food poisoning

– Meat-based recipes from all 36 countries called for an average of 3.9 spices, significantly more than 2.4 spices in average vegetable recipes

More spices in hotter areas

• Prediction 5: Within a country, recipes from lower latitudes and altitudes should be spicier than higher latitudes and altitudes– Difficult to find recipes tied to altitude– In US and China, recipes from southern latitudes

used a greater variety of spices and spices used more often

– Southern recipes contained spices more likely to kill or inhibit bacteria

Alternate Hypotheses

• Spices disguise the smell and taste of spoiled foods - ignores dangers of spoiled meats which could be deadly

• Spices used as medicines - dosage is different and all people use the food

• Spices used in hotter climates because it helped increase perspiration (only works for chilis and horseradish)

• Spices used because they taste good - some spices initially distasteful - yet people continue to use

References

• Billing, J. and P. Sherman. 1998. Antimicrobial functions of spices: why some like it hot. Quarterly Review of Biology, 73: 3-49.

• Sherman, P. amd J. Billing. 1999. Darwinian Gastronomy:Why We Use Spices. BioScience. 49 (6): 453-462

• Sherman, P. and S. Flaxman. 2001. Protecting Ourselves from Food. American Scientist, 89: 142-151