This is a presentation given at the UAE Health Authority sponsored TCAM conference in Abu Dhabi in 2013. The title of the talk was: "From the field to the pharmacy: The important role of TCAM to the future of public health" Abstract: Ethnobotanical studies concerning knowledge and use of TCAM are critical for laying the groundwork for both pharmaceutical development and public health policy. In this talk, I will review some of the translational aspects of medical ethnobotany research, highlighting the importance of documenting local knowledge of TCAM practices and investigating the efficacy, safety and potential for broader public health applications (i.e. herbal supplements and pharmaceuticals). Methodology for implementation of such studies will be reviewed and potential applications of the data in UAE public health policy and practice will be discussed.

1. 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

2. Overview
• Ethnobotany
• Medical Ethnobotany in the UAE
• Education and Outreach
• Herbarium and Biocultural Collections
• Drug Discovery
• Conclusions

3. 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

4. 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.

5. The Ethnobotanical Approach

6. • 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

7. Environmental Zones
• Deserts
• Oases
• Mountains
• Coastal
regions

8. 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

9. 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

10. 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

11. 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

12. Ethnobotanical Approach to Drug Discovery
TEKofmedicinalplants
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.

13. 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

14. 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

15. Deter other
plant species
from growing
nearby
Fight off
microbial
invasion/infection
Attract pollinatorsDefense against
herbivory
Secondary Metabolites

16. 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

17. 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

18. 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

19. Models for Biofilm Formation & Dispersal
microtiter plate
catheters in vivo
(Imaging with IVIS)flow cells
catheters in vitro

20. 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.

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

22. 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

23. 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.

24. 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.
0
500000
1000000
1500000
2000000
2500000
3000000
3500000
4000000
4500000
5000000
0 8 16 32 64 128
Concentration (μg/ml)
PeakArea
δ-hemolysin
C

25. Implications for Drug Discovery
Biofilms
Quorum
sensing
Efflux
pumps
Immune
adjuvants
Synergy
Conjugation
Single drug/single target
Bacteriostatic
Bactericidal
Clinically
relevant
isolates
Systems
biology

26. 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

27. 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