FROM THE FIELD TO THE PHARMACY: The important role of TCAM to the

future of public health

Cassandra L. Quave, Ph.D.

Department of Dermatology, Emory University School of Medicine

Center for the Study of Human Health, Emory College of Arts & Sciences

http://etnobotanica.us/

cquave@emory.edu

Overview

• Ethnobotany

• Medical Ethnobotany in the UAE

• Education and Outreach

• Herbarium and Biocultural Collections

• Drug Discovery

• Conclusions

Role of TCAM in Public Health

Traditional Ecological Knowledge, Product Samples, Herbarium Specimens, Use data, Consensus Indices

Imported TCAM

Practices

National TCAM

practices

Botanical, Mineral &

Animal Products

Drug discovery, Safety, Efficacy, Public outreach and education

Ethnobotany

Ethnobotany

• Ethnobotany is the study of the interactions and relationships between plants and people over time and space. This includes the uses, knowledge, beliefs, management systems, classification systems and language that both modern and traditional cultures have for plants and their associated terrestrial and aquatic ecosystem.

• Thus, ethnobotany is the science of survival.

Ethnobotany, the science of survival: a declaration from Kaua‘i. Economic Botany 61:1-2. 2007.

The Ethnobotanical Approach

• Layers of Consent: – IRB – Prior informed consent – Country & community

agreements – Plant permits

• Data Collection: – Semi-structured

interviews – Focus groups – Participant-observation

• Biological Sampling – Voucher collection – Bulk specimen collection

Methods: Ethnobotanical Research

Environmental Zones

• Deserts

• Oases

• Mountains

• Coastal regions

Target Populations – Legacy Project

• Interviews with TCAM specialists/practitioners in various environmental zones

• Interviews with household TCAM users/practitioners – Focus on: agricultural and rural regions & elderly population

• Market surveys – focus on sale of local plants, minerals, animal products

– “New” TCAM • Large diversity in TCAM practices and materials imported with

immigrant waves – Interviews/surveys with immigrants representing different regions (i.e.

Indonesia, Pakistan, India, etc.)

– Follow with safety studies (focusing on adverse event reports)

• Market surveys – Focus on sale of imported products and plants

Key Data to Collect in Legacy Project Research

TEK

• Local name(s)

• Scientific name

• Harvest time

• Cultivation status (or if acquired at market)

• Photographs

• Herbarium specimen

• Part(s) used

• Mode of preparation

• Mode of application

• Dose & duration of treatment

• Toxicity or side effects

• Food or medicinal food uses

• Ritual use or role in folklore

• Ethnoveterinary applications

• Mode of knowledge transmission

Education & Outreach • Current practices:

– Encyclopedia of Medicinal Plants – Workshops – Herbarium displays – Safety monitoring

• Future Directions? – Digitized herbarium – Biocultural collections related to

TCAM and health – Ethnobotany of UAE

• Academic research • Text for the public

– Phytochemical/biological studies: • Validation of therapies • Safety studies • Verification of plant identity in

imported supplements & goods

ZCHRTM Herbarium

• Represents diversity of UAE species

• Physical specimens used in educational initiatives

• Future Directions? – Herbarium website – Biocultural collections – Digitized collection

• Applications for university research & education

• Public outreach & education • Create opportunities for

international collaboration

Ethnobotanical Approach to Drug Discovery TE

K o

f m

edic

inal

pla

nts

Field collections

Herbarium specimens

Add to digitized & physical collection

Educational outreach initiatives

Bulk Specimens Perform

extractions

In vitro bioassay-guided fractionation

TEK validation

Safety studies

Isolation/Elucidation of active or marker

compounds

Animal efficacy studies

Safety studies

TEK validation

“The ethnobotanical approach [to drug discovery] assumes that the indigenous uses of plants can offer strong clues to the biological activities of those plants.”

Cox & Balick. Scientific American. June 1994, pp. 82-87.

Why look to plants for new medicines?

• Natural botanical products:

– Have rich structural diversity, chirality, and extensive functional group chemistry

– Are likely produced by the plant to fill a specific need (i.e. defense against pathogens)… potential for efficacy against human pathogens

• Ethnobotanical-directed study of plants used for medicine is often more effective than a random approach

Secondary Metabolites

• Organic compounds not directly involved in basic survival of the organism (growth, development, or reproduction)

• In plants, these are used for: – Defense against predation and herbivory

– Competitive “warfare” with other organisms in the community

– Pollinator attractors

– Dispersal

– Responsible for plant colors, flavors, and odors

Deter other

plant species

from growing

nearby

Fight off

microbial

invasion/infection

Attract pollinators Defense against

herbivory

Secondary Metabolites

Culturally-Relevant Approach to Drug Discovery

• Base on TEK-directed screening has implications for: – Extraction protocols – Bioassays/targets for

screening

• Focus on UAE health priorities – NCDs

• Obesity • Diabetes • CVD • Cancer

• Global priorities – Infectious disease

• Antibiotic resistance

Injuries 21%

Communicable, maternal,

perinatal and nutritional conditions

13%

Other NCDs 11%

Diabetes 3%

Respiratory conditions

2%

Cancers 12%

CVD 38%

Proportional Mortality (% of total deaths, all ages) NCDs estimated to account for 67% of all deaths

WHO, NCD Country Profile, 2011

Global Entry into the Post-Antibiotic Era

• Acquired versus intrinsic resistance (biofilms)

• Alarming statistics: – 440k new cases of MDR-

TB/year = 150k fatalities

– S. aureus kills ~19k/year in US

– 17M new biofilm infections/year in US = 550k fatalities

– Shigella and N. gonorrhoeae on last-line therapies

– New lineages of MDR Klebsiella emerging

• Economic burden of HAI’s in US = $28.4-45B

Example of ethnobotanical approach to drug discovery for new anti-infectives: 220D-F2

• Traditional uses in S. Italy:

– Leaves: furuncles, abscesses, and other skin inflammations

– Roots: hair loss – Fruits: eaten fresh and in

marmalades

• One of 116 remedies related to SSTIs and other topical dermatological treatments identified

• 168 extracts screened • Anti-biofilm activity first

identified & published in 2008 and # 220 marked as possible lead

Elmleaf Blackberry; Rubus ulmifolius Schott. (Rosaceae)

Quave et al. Journal of Ethnobiology & Ethnomedicine. 2008. 4(5)

Quave et al. Journal of Ethnopharmacology. 2008. 118:418-428

Models for Biofilm Formation & Dispersal

microtiter plate

catheters in vivo

(Imaging with IVIS) flow cells

catheters in vitro

Example: Biofilm Inhibitor 220D-F2

Quave et al., PLoS One. 2012: 7(1)

220D-F2 (derived from Rubus ulmifolius) is effective against all clonal lineages of S. aureus, regardless of antibiotic resistance profile and nontoxic to mammalian cell lines.

Biofilm Inhibitor: 220D-F2

220D-F2 improves response to functionally distinct classes of antibiotics, including daptomycin, clindamycin, vancomycin, and oxacillin.

220D-F2 Anti-streptococcal Activity

C

Activity against the pneumococcus (Streptococcus pneumoniae). A. 220D-F2 kills planktonic cells. B. 220D-F2 disperses biofilms and kills cells. C. 220D-F2 demonstrates potent antibacterial activity against planktonic and biofilm associated S. pneumoniae.

Talekar et al. (In review) PLoS One

Another target: Quorum sensing and the agr system

Quave et al. 2010. Planta Medica 76:1-8.

168 extracts screened for QSI activity at sub-MIC doses yielded 3 potential leads. Extract 134 was the most promising due to its lack of mammalian cytotoxicity and efficacy against agr types I-IV.

QSI activity observed in agr Types I-IV

Extract 134 quenching of agr system function in S. aureus using P3-GFP reporters. A.

Dose-response test in USA300 (agr Type I) for IC50 determination. MW2 refers to a control

inhibitory AIP. B. Dose-response testing across agr Type I, II, III, and IV strains. C. Dose-

response in production of delta-toxin, a RNAIII-translational product.

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Concentration (μg/ml)

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Implications for Drug Discovery

Biofilms

Quorum sensing

Efflux pumps

Immune adjuvants

Synergy

Conjugation

Single drug/single target Bacteriostatic Bactericidal

Clinically relevant isolates

Systems biology

Conclusions

TCAM: documentation &

study

Drug Discovery & Safety studies

Education/Outreach

• Documentation of TCAM is a priority for: – Preservation of UAE

traditions and history (for national TCAM)

– Safety/ public health monitoring (esp. for “newly introduced” TCAM

– Drug discovery leads • In-house research

• Strategic collaborations

– Outreach/Education

Public Health in UAE

Research Acknowledgements

People • Collaborators: Dr. Andrea Pieroni (UNSIG, Italy), Dr. Brad

Bennett (FIU), Dr. Lisa Plano (Univ. of Miami), Dr. Michael Otto (NIH/NIAID), Dr. Mark Smeltzer (UAMS), Dr. Cesar Compadre (UAMS), Dr. Alex Horswill (Univ. of Iowa)

• All of the study participants in the Mediterranean

• Emory Mentors and Collaborators: Dr. Michelle Lampl, Dr. Dennis Liotta, Dr. Jorge Vidal, Dr. Sharmilla Talekar, Dr. Bill Shafer, Dr. Maira Goytia, Dr. David Weiss, Dr. Phil Rather, and Dr. Jack Arbiser

• Current Lab Team: Kate Nelson, Parth Jariwala, Janessa Aneke, Sam Anderson, Boru Wang, Samir Hussaini, Sandy Jiang, Michelle Paine, Matt Dorian, Sarah Meadows, Paula Tyler, and Amelia Muhs

Funding Sources • National Institutes of Health, National Center for

Complementary and Alternative Medicine (PI: Quave) – R01 AT007052

– F32 AT005040

– F31 AT004288

• Georgia Research Alliance – GRA.VL13.C7 (Phase IA & IB)

• Center for the Study of Human Health