ECOPHARMACOGNOSY AND THE

GLOBALIZATION OF TRADITIONAL
MEDICINE

Salvia miltiorrhiza Matricaria chamomilla Schisandra chinensis

Geoffrey A. Cordell
Natural Products Inc, Evanston, IL

Planta Med., 77, 1129-1138 (2011)

Chem & Eng News, June 27, 52-56 (2011)
Phytochem. Lett. 4, 391-398 (2011); J. Nat. Prod., 75, 514-525 (2012)
 LECTURE
OUTLINE

• Questions
• Current Status
T.A.R.D.I.S. • Globalization
• Sustainable Medicines
• Future Strategies
• Conclusions
London, Marrakech,
England Morocco
 SOME QUESTIONS FOR TM
• How SUSTAINABLE is Traditional Medicine
(wild-crafting vs. cultivation)?
• What are the implications of population
growth, globalization, and climate change?
• What is the contemporary science behind the
TMs being provided to the patient?
• How can the ethnomedical information and
biological resources be conserved and
developed for the health of future generations?
 MORE QUESTIONS FOR TM

• What is the role for safe and effective TMs

within integrated health care? PolyRx?

• What communications and education are

needed for practitioners, patients, and
educators about the new era of TM?

• What is the agenda for the next 15-20 years

for accessible, safe, effective, and
SUSTAINABLE TM products globally?
 TRADITIONAL MEDICINE – HAS IT
CHANGED IN 4000 YEARS?

Painting depicting a TCM Medellin, Colombia, 2006

Practitioner, 2000 B.C.

We must do better! It’s a Patient Expectation!

 Marrakech, Morocco

Kerman, Iran CONTEMPORARY Valparaiso, Chile

TRADITIONAL
MEDICINE

Juiz de Fora, Yogyakarta,

Brasil Lijiang, China Indonesia
 TCM
TODAY
TRADITIONAL MEDICINES –THE
PATHWAY FROM CRUDE DRUG
TO STANDARDIZED PRODUCT

Based in Science
 State of the Planet Declaration,
“Planet under Pressure” Conference
London, March 29, 2012

• “The continuing function of the Earth system

as it has supported the well-being of human
civilization in recent centuries is at risk”
• Warns of “a humanitarian emergency on a
global scale”
State of the Planet Declaration
Calls for:

• Transformation in values, beliefs, and

aspirations towards sustainable prosperity

• A new contract between society and the

sciences

• Enhanced capacity-building and

environmental observation systems
THE NEW CONTRACT BETWEEN
SOCIETY AND THE SCIENCES
Needs to Encompass:

• Global sustainability analyses based in

science
• Integrated, international, and solutions-
oriented research, implemented and
involving government, society, scientists,
and the private sector
• Enhanced dialog on issues of global
sustainability
 GLOBAL SUSTAINABILITY
Sustainability is the
journey we are all on.

It is the economic and scientific

ethos that harnesses human
creativity for the benefit of
future generations by limiting
the contemporary depletion of
Earth’s resources.

It is the fabric and foundation of

contemporary society
 WHO DIRECTOR GENERAL,
DR. MARGARET CHAN:

Drug resistance to antibiotics:

“could bring the end of modern
medicine as we know it.”

Copenhagen, March 16, 2012

Chem & Eng News June 27, 52-56 (2011)
 CHALLENGES FOR A
COUNTRY

How to balance importation of

allopathic drugs, developing a
pharmaceutical industry, generic
substitution, and providing safe and
effective traditional medicines in a
SUSTAINABLE and affordable manner
 WHAT ARE THE
IMPLICATIONS FOR
TRADITIONAL MEDICINE?

Traditional Medicine will only remain relevant

if it meets societal needs in health care,
and in care of the environment,
in a sustainable manner
 ECOPHARMACOGNOSY

- A DEFINITION

“The study of sustainable,

biologically active natural resources”
 GLOBALIZATION OF
TRADITIONAL MEDICINE

Since the Silk Road,

traditional medicines
have been an integral
aspect of global
commerce, now the
practices are also being
globalized
 THE SILK ROAD

• China sent silk, iron utensils, ginger, cinnamon,

and rhubarb
• Pepper, malabathrum, spikenard, costus, indigo,
and eventually opium traded eastward
 BIG PHARMA R&D 2012 –
A NEW PICTURE EMERGES
• Pfizer: $11 bn R&D in 2009, $8.5 bn in 2012
• Loss of Rx Patents: $32bn lost in sales in
2011
• More diverse collab. Industry and academia
• Smaller research units. Narrower res. focus:
antivirals, oncology, metabolism, CNS,
inflammation
• No research on: anemia, bone health,
obesity, GI disease, infectious diseases,
drug resisitance, etc.
L.M. Jarvis, C&E News June 7, 13-18 (2010)
STRATEGIC DIRECTIONS FOR
THE NATURAL PRODUCT
SCIENCES

Form follows Function

What is the Function for Natural

Products Research in examining,
delineating, and articulating, the niche
for natural products and traditional
medicine in future global health care?
 “Would you tell me,
please, which way I
ought to go from here?”
asked Alice.

“That depends a good

deal on where you want
to get to,” said the Cat.

BLTC PRESS
 SIX MYTHS OF TRADITIONAL
MEDICINE
• This traditional medicine has been
used for thousands of years (ergo
safe and effective)
• Using the “right” plant is enough for
effectiveness
• The constituents are always the same
• Older plant material is less effective
(or more toxic)
• This product is well-regulated
• The plant will always be there

Where is the scientific evidence?

 CREATING A VISION FOR
NATURAL PRODUCTS
• Natural Products must contribute to
health care maintenance and food and
nutritional science – stay relevant
• Create a sustainable vision for
intellectual property, information
systems, chemistry, biology,
technology, and biotechnology
• Create alliances locally and globally
 OPPORTUNITIES FOR
ECOPHARMACOGNOSY
DEVELOPMENT - I

• New medicinal products

• New nutraceutical products
• New cosmetic products
• New enzyme-based processes for the synthesis of
bulk chemicals and medicinal agents

• What are the investment needs for research and

infrastructure development?
• Where, globally, are the economic opportunities?
 OPPORTUNITIES FOR
ECOPHARMACOGNOSY
DEVELOPMENT - II
• Quality Control of TMs - a scientific and regulatory
continuum

• Innovation of new TMs (Are all the plants needed?)

• Diseases with no available drugs, incl. local diseases

• Diseases for which there is drug resistance
• Diseases for which drugs are available globally,
but which are too costly or not locally available
WPRO STRATEGIC DIRECTIONS FOR
TRADITIONAL MEDICINE –
FUNDAMENTAL PHILOSOPHY

• Patients should be assured of

the continued availability of
quality, safe, and effective
traditional medicine products
and practices based on the
results of evidence-based
research
 WPRO STRATEGIC
DIRECTIONS FOR
TRADITIONAL MEDICINE - I

• Develop policies, regulatory criteria,

and technical guidelines for safe and
effective TMs, including for all
contaminants and adulterants

• Harmonize regulations, terminology,

and develop international standards
for TM products and practices
 WPRO STRATEGIC
DIRECTIONS FOR
TRADITIONAL MEDICINE - II

• Develop resource inventory and

conservation programs to assure the
Sustainability of natural health
materials

• Develop globally accessible databases

on ALL aspects of TM
 INTER-RELATIONSHIPS IN TM

INTERNAT
SCIENCE
STANDS

POLICIES,
TECHNOLOGY
REGS

PRACTITIO- COMMUNIC
NERS -ATION

INDUSTRY
Ecopharmacognosy
is at the center
of these interactions
SUSTAINABLE MEDICINES
 QUALITY CONTROL - A
GLOBAL ISSUE
• Quality control of most traditional medicines
sold around the world is poor or non-existent

• Patients need to be assured of accessibility,

quality, safety, efficacy, consistency, and
shelf-life

• Quality control is a continuum, and must be

evidence-based in contemporary science
 A RECENT TM INCIDENT

The Star, Oct 4, 2012

Up to 25% of TM products may be contaminated

 WHAT IS NEEDED TO ADVANCE
TRADITIONAL MEDICINE?
• Vision and leadership at the national and
international level – a “voice”
• Cooperation between Govt., Academia, and
Industry for staged program development
• $$$$$$
• Well-designed and prioritized botanical,
chemical, biological, and clinical studies
• Effective communication of results
• Assuring patient accessibility to safe and
effective TMs and phytotherapeuticals
THE FOUR PILLARS OF TM
QUALITY CONTROL
• Information
• Botany
• Chemistry
• Biology
All built on the foundations of
SUSTAINABILITY and ACCESSIBILITY
TRENDS IN TCM FOR 2030
• GLOBALIZATION
• SCIENTIFICATION
• RATIONALIZATION
• HARMONIZATION
• INTEGRATION
 GLOBALIZATION OF TCM

• Stated Government Policy since 2005

• Products sold all over the world
• Practitioners educated in many
countries (standard curriculum)
• Plants grown in Africa, S. America,
and Australia
• Very different from Kampo or
Korean TM
TCM INDUSTRY

• Over
 SCIENTIFICATION OF TCM
• Information systems
• Standardization based on plant DNA
identification and chemically and
biologically known active principles
• Studies of safety and efficacy in vitro, in
vivo, and in humans
• Genetic implications based on systems
biology
• GAP, GLP, GMP, and GCP certifications
TCM PRODUCTS IN CLINICAL
TRIALS AT US FDA

• Danshen Dripping Pill, angina

• Kanglaite injection, cancer
• Xuezhikang capsule, hyperlipidemia
• Fuzheng Huayu capsule, liver fibrosis
• Nongsuo Denggui Pill, thrombosis
 MALAYSIAN PLANTS OF
CURRENT INTEREST - I

Eurycoma Phyllanthus Orthosiphon Labisia Andrographis

longifolia amarus stamineus pumila paniculata
(Simaroubaceae) (Euphorbiaceae) (Lamiaceae) (Myrsinaceae) (Acanthaceae)

tongkit ali dukung anak misai kucing kacip fatimah hempedu bumi
 MALAYSIAN PLANTS OF
CURRENT INTEREST - II

Centella Ficus Morinda Hibiscus Clinacanthus Zingiber

asiatica deltoidea citrifolia sabdariffa nutans officinale
(Apiaceae) (Moraceae) (Rubiaceae) (Malvaceae) (Acanthaceae) (Zingiberaceae)

pegaga mas cotek mengkudu roselle belalai gajah halia

INTELLECTUAL PROPERTY ISSUES
 MULTITARGET THERAPY
AND SYNERGY
• Current therapeutic strategy for cancer
and HIV/AIDS
• Established for traditional medicine
• Multiple chemicals in an extract reflect
multiple targets and mechanisms
• Evaluate synergistic (and antagonistic)
effects of extracts and compounds (and
OTC and Rx products)
REMOTE DETECTION OF NATURAL
PRODUCTS IN THE FIELD

Handheld Raman Handheld FT-IR

Instrument Instrument
BIOTECHNOLOGY DEVELOPMENT
FOR SECONDARY METABOLITES

• Chemical analysis typically represents a

“phytochemical moment” in time; NOT the
metabolic capacity of a plant. Very important in
considering TM quality control. Need a
“phytochemical video”

• Modulating genes in a controllable manner will be

important in traditional medicine reproducibility

• Critical to maintain the genetic capacity of

medicinal plants through conservation, botanic
garden development, germplasm storage
 DEVELOPMENT OF
PLANT ENZYMES
• Unlike microbial enzymes, the genes for
plant enzymes are not clustered in one place
• Secondary metabolism in plants is therefore
scattered within plant cells
• Can the genes of plant secondary metabolite
biosynthesis be gathered and linked to form
a cohesive pathway?
• Can plants be genetically mined for dormant
metabolic pathways?
 DYNAMIC
BIOSYNTHESIS

• Chemical analysis of a plant or microorganism

typically represents a “phytochemical moment”
or a “microbial moment” in time; NOT the full
metabolic capacity of a plant or microorganism

• Need a “phytochemical video” to envision

secondary metabolite flux in a dynamic manner
 CONCLUSIONS
• Maintenance and restoration of existing
global biodiversity is critical for a healthy
people and a healthy Earth

• Collaborative Natural Products research

must pursue SUSTAINABLE resources
and practices, incorporate contemporary
technologies, and stay relevant to societal
needs for new medicinal, cosmetic, and
nutraceutical agents
THANK YOU!!
 BESIDES TRADITIONAL
MEDICINES ARE THERE OTHER
APPROACHES?

ARE MEDICINES IN THE DIET

AN ECONOMIC OPPORTUNITY?

A DRUG DISCOVERY
OPPORTUNITY?
SPICE, NUTRIENT, MEDICINE??
Turmeric

Cinnamon

Ginger
SPICE, NUTRIENT, MEDICINE??

Black
pepper

Oregano

Garlic
 HOW ARE MEDICINAL
PLANTS USED GLOBALLY?
• Ca. 450,000 tonnes of
medicinal plants in
commerce annually
• Est. 25,000 – 40,000 plant
species
• At least 85% harvested from
wild collections
• From a public health care
perspective that is not
SUSTAINABLE
WHO ARE THE TRADERS?
• 80% of trade is between 12 countries

• Major Exporters: China, Hong Kong,

India, Mexico

• Major Importers: Hong Kong, USA (from

India), Japan (from China), Germany
(from Bulgaria)

• Trading Centers: USA, Hong Kong, and

Germany
9,000 Medicinal Plant species are threatened
 THE NEW TRADE ROUTES
FOR MEDICINAL PLANTS

Santiago, Chile Chengdu, PRC

• Traditional Medicines

• Illicit Plant Products

 ILLICIT PLANT USE –
GLOBAL VIEW

• Opium Market: $68 bn;

Cocaine Market: $85 bn in 2010

• 200,000 ha of opium grown in 2010,

150,000 ha of cocaine cultivation

• 16.5 m cocaine users/year;

same # of heroin/opium users
World Drug Report, 2011
DRUG TRAFFICKING ROUTES

Illegal drug trafficking is valued at

about 0.9% of global GDP
 COCAINE SUBMARINES

• 60 ft long, carry 4-5 people

• 5,000 mile range at 13 knots
• Carry ca. 7 tons of cocaine, valued
at $200 million
• Over 120 sightings in 2011 off
Mexico and Central America
on both coasts
COCAINE AND
COCA-COLA

• Over
GLOBALIZATION OF COCA-COLA
• Developed in 1885, Coca-Cola is now sold in
253 out of 257 countries in the world
• Cocaine removed from Coke in 1904
• Leaves from Peru still processed in NJ (??)
• Kola nuts (Cola acuminata) – chewed in many
W. African countries - no longer in Coke
 WHAT IS GLOBAL HEALTH?

Recognizes that:

Access to Health Care

is a Human Right

A Healthy People
Require a Healthy Earth
 INTEGRATION OF TCM

• Integrating Chinese and Western

Medicine in a more (w)holistic
approach to health care, for both
prevention and treatment
• Employing a poly Rx approach for
improved health care outcomes
• Personalized health systems
• Establishing drug-drug interactions
 TRADITIONAL MEDICINE –
GLOBAL USE GUESSTIMATE
• Over 64% of world’s population (ca.
4.5 bn) use plants as a primary
health care source

• Needs to be scientifically established

as a SUSTAINABILITY issue

Akerele et al., Bull. WHO 63, 965 (1985)

 A VISIONARY QUOTE

“If you are on the fifth

step and you think you
are too high, you will
never make it to the
sixth step.”

Ajahn Chah,
A Still Forest Pool