Plants used to treat infectious disease - III

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

2. Plant Products • Long history of use as antimicrobials • Very few have made the transition from herbal remedies to mainstream drugs • Often much weaker than antibiotics • Renewed interest largely due to antibiotic resistance

3. Chaulmoogra Oil

4. Leprosy - Hansen’s Disease • Chronic skin disease endemic to tropical and subtropical areas • Caused by bacterium, Mycobacterium leprae • 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 • Apparently two forms • Tuberculoid type may be limited to a few nerves and skin area • Lepromatous type is disseminated throughout the body

5. 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 • US leper colony in Carville LA

6. Hansen’s disease in 2002 • 763,917 new cases detected worldwide • 96 cases occurring in the United States • WHO listed Brazil, Madagascar, Mozambique, Tanzania, and Nepal as having 90% of cases • Worldwide: 1-2 million persons are permanently disabled as a result of Hansen's disease

7. Chaulmoogra Oil • Mentioned in the Hindu Vedas over 2000 years ago as helping in curing leprosy • Oil reached Europe in the mid-nineteenth century, but source was 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 used in 1946

8. Chaulmoogra Oil • Earlier use in Hawaii • Alice Ball (1892-1916) worked on chaulmoogra oil to treat leprosy • Died in 1916 (24 yrs old) - work was taken over by Arthur Dean who initially got credit for work with chaulmoogra oil

9. Chaulmoogra Oil • Source: seeds of Hydnocarpus wightiana and Hydnocarpus anthelmintica is triglyceride of fatty acids containing cyclopentenyl group • Given by injection to patients with leprosy • Symptoms went away and bacteria disappeared from nasal secretions but relapse often occurred • Early cases were completely cured • More established cases had relapse • Today standard treatment is combined drug therapy – 3 antibiotics: dapsone, rifampin, and clofazimine

10. Herbal Remedies

11. 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

12. Berberine containing herbals and plant part used

13. Berberine research on-going • Much of the research focused on its use in cases of diarrhea, including that caused by Vibrio cholerae and Escherichia coli • In one study, berberine had antimicrobial activity against gram-positive and gram-negative bacteria, fungi, and protozoa • Berberine has been also shown to inhibit HIV-1 reverse transcriptase

14. Berberine as an antimicrobial • Activity still weak compared to antibiotics • Possibly do to MDR pumps in bacterial cell membranes • Research focus on MDR inhibitors in Berberisfremontii and other species of berberine containing plants

15. Herbs and Spices

16. 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

17. Essential Oils • Value of herbs and spices due to essential oils • Most commonly found in leaves, flowers, and fruits where they occur in glandular trichomes • Chemically, essential oils are most commonly terpenes, but may be phenolics

18. History of spices • Early history • Ebers Papyrus • Ancient Greece and Rome • Dark Ages • Venice and Genoa – Marco Polo • Prince Henry of Portugal • Age of Exploration • 16th to 19th centuries

19. 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

20. 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?

21. Predictions based on spice use • Sherman and his students developed an 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

22. 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

24. 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)

26. 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 bacteria • Sherman et al looked at effectiveness of native recipes in killing 30 common food-borne bacteria • As annual temp increased, the estimated percent of bacteria that would be inhibited also increased

27. More spices used with meats • Prediction 4: Within a country meat recipes should be spicier 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

29. 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

30. 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