Plants used to treat infectious disease - III

Plant Products as Antimicrobial Agents

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

Chaulmoogra Oil

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

Hansen’s disease in 2004

407,791 new cases detected worldwide Around 100 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

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

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

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

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 and plant part used

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 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

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 Berberis

fremontii and other species of berberine containing plants

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

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

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

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 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

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

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 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

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

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