Plants used to treat infectious disease - III

1. Plants used to treat infectious disease - III Plant Products as Antimicrobial Agents

2. 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

3. 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

4. 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)

5. 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

6. 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.

7. 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

8. 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

9. 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

10. 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

11. 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

12. Herbal Remedies

13. 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

14. Berberine containing herbals

15. 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

16. Herbs and Spices

17. 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

18. 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

19. 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

20. 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

21. 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)

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. 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?

31. 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

32. 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

33. 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

35. 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)

36. 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

37. 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

39. 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

40. 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

42. 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

43. 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

44. 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. AmericanScientist, 89: 142-151