Upload
cassandra-quave
View
342
Download
0
Embed Size (px)
Citation preview
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/
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.
0
500000
1000000
1500000
2000000
2500000
3000000
3500000
4000000
4500000
5000000
0 8 16 32 64 128
Concentration (μg/ml)
Pe
ak
Are
a
δ-hemolysin
C
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