Download DOC - Knowledge for development

Ethnobotany and the Future of R&D on Indigenous Plant
Resources
Ameenah Gurib-Fakim, CEPHYR, 7th Floor, Cybertower2, Ebene,
Mauritius
[email protected]
The term ‘Ethnobotany’, used by Harshberger in 1896, was defined as the
study of “plants used by primitive and aboriginal people”. Years later,
Jones (1941) advanced a more concise definition: ‘‘The study of the
interrelationships of primitive men and plants.” Schultes (1967) expanded
this to include “the relationships between man and his ambient
vegetation”. Ethnobotany and ethnopharmacology are interdisciplinary
fields of research that look specifically at the empirical knowledge of
indigenous peoples concerning medicinal substances, their potential
health benefits and the health risks associated with such remedies
(Schultes and Von Reis, 1995).
Plants have formed the basis of sophisticated traditional medicine systems
that have been in existence for thousands of years and continue to
provide mankind with new remedies. Although some of the therapeutic
properties attributed to them have proven to be erroneous, medicinal
plant therapy is based on empirical findings over hundreds and thousands
of years. Yet interest in potential chemotherapeutic agents continues. The
importance of ethnobotanical inquiry as a cost-effective means of locating
new and useful tropical plant compounds cannot be overemphasized.
Approximately half (125,000) of the world’s flowering plant species live in
the tropical forests (World Conservation Monitoring Centre, 1992). While
Brazil has some 55,000 species of plants, scientific reports exist for only
0.4% of the flora. Tropical rainforests continue to support a vast reservoir
of potential drug species. They provide scientists with invaluable
compounds to be used as starting points for the development of new
drugs. The potential is enormous, as to date only about 1% of tropical
species have been studied for their pharmaceutical benefits (Jachak and
Saklani, 2007). The existence of undiscovered pharmaceuticals for
modern medicine has often been cited as one of the most important
reasons for protecting tropical forests, so the high annual extinction rate
is a matter for concern, to say the least. To date, about 50 licensed drugs
have come from tropical plants (Burslem et al., 2001). Modern medicine
usually aims to develop a patentable single compound or a ‘magic bullet’
to treat a specific condition (Farnsworth et al., 1985).
Many of the plant-derived pharmaceuticals and phytomedicines currently
in use today were traditionally used by native people around the world.
Some of this knowledge has been documented and codified or studied
scientifically. Medicinal plants typically contain mixtures of different
chemical compounds that may act individually, additively or in synergy to
improve health. A single plant may, for example, contain bitter substances
that stimulate digestion, anti-inflammatory compounds that reduce
swellings and pain, phenolic compounds that can act as an antioxidant
and venotonics, antibacterial and antifungal tannins that act as natural
antibiotics, diuretic substances that enhance the elimination of waste
products and toxins and alkaloids that enhance mood and give a sense of
well-being.
While European traditions are particularly well known and have had a
strong influence on modern pharmacognosy in the West, almost all
societies have well-established customs, some of which have hardly been
studied at all. Importantly, the vast majority of people on this planet still
rely on their traditional materia medica (medicinal plants and other
materials) for their everyday healthcare needs and according to the World
Health Organization (WHO, 1999), over 80% of the world’s population
(primarily in developing countries) rely on plant-derived medicines for
their healthcare.
The study of these traditions not only provides an insight into how the
field has developed but it is also a fascinating example of our ability to
develop a diversity of cultural practices. Traditional medicine often aims to
restore balance by using chemically complex plants, or by mixing together
several different plants in order to maximize a synergistic effect or to
improve the likelihood of an interaction with a relevant molecular target.
In most societies today, allopathic and traditional systems of medicine
occur side by side in a complimentary way. The former treats serious
acute conditions, while the latter is used for chronic illnesses, to reduce
symptoms and improve the quality of life in a cost-effective way.
People who use traditional remedies may not understand the scientific
rationale behind their medicines, but they know from personal experience
that some medicinal plants can be highly effective if used at therapeutic
doses. Since we have a better understanding today of how the body
functions, we are in a better position to understand the healing powers of
plants and their potential as multi-functional chemical entities for treating
complicated health conditions.
Modern allopathic medicine has its roots in ancient medicine, and it is
likely that many important new remedies will be discovered and
commercialized in the future, as they have been up to now, by following
the leads provided by traditional knowledge and experiences. It is
estimated that natural products and their derivatives represent more than
50% of all the drugs in clinical use in the world. Medicinal plants
contribute no less than 25% of the total (Balandrin et al., 1993). Potent
drugs derived from flowering plants include Dioscorea-derived diosgenin,
from which all anovulatory contraceptive agents have been derived;
pilocarpine to treat glaucoma and dry mouth, derived from a group of
South American trees (Pilocarpus spp.) in the Citrus family; two powerful
anticancer agents from the Madagascan rosy periwinkle (Catharanthus
roseus); laxative agents from Cassia sp. and a cardiotonic agent to treat
heart failure from Digitalis species.
Over the past few years, a large number of lead molecules have come out
of the traditional ayurvedic system of medicine and include Rauvolfia
alkaloids for hypertension, psoralens for vitiligo, Holarrhena alkaloids for
amoebiasis, guggulsterones as hypolipidaemic agents, Mucuna pruriens
for Parkinson’s disease, piperidines as bioavailability enhancers, bacosides
for mental retention, picrosides for hepatic protection, phyllanthins as
antivirals, curcumine for inflammation, with anolides and many other
steroidal lactones and glycosides as immunomodulators. There is also
growing evidence to show that old molecules are finding new applications
through a better understanding of traditional knowledge and clinical
observations. For example, forskolin or coleol, the labdane diterpene from
Coleus forskohlii, has been revisited as adenalyted cyclase activator to
treat obesity and atherosclerosis. Similarly, antimicrobial berberine
alkaloids are being investigated for potential in treating dyslipidaemia, and
involve a mechanism different from statins (Levoye and Jockers, 2008).
Of the drugs approved between 1981 and 2002, 60% of anticancer and
75% of anti-infective drugs could be traced to natural origins (Newman et
al., 2003). Although discovered through serendipitous laboratory
observation, three of the major sources of anti-cancer drugs on the
market or completing clinical trials were derived from North American
plants used medicinally by native Americans: the pawpaw (Asimina spp.;
the western yew tree (Taxus brevifolia), effective against ovarian cancer;
and the mayapple (Podophyllum peltatum), used to combat leukaemia,
lymphoma, lung and testicular cancer (Cragg and Newman, 2005).
A multidisciplinary approach combining natural product diversity with
combinatorial synthetic and biosynthesis methods may prove particularly
effective. Combinatorial chemistry approaches based on natural products
from traditional medicine are being used to create screening libraries to
identify agents that closely resemble drug-like compounds. Since most of
these compounds are part of routinely used traditional medicines, their
tolerance and safety are relatively better known than other synthetic
chemical entities entering first in-human studies.
The traditional knowledge-inspired pharmacology related to reversing the
routine ‘laboratory-to-clinic’ progression of new drugs to a ‘clinic-tolaboratory’ progression. Reverse pharmacology is increasingly being
studied and is the rigorous scientific approach of documenting clinical
experiences and experiential observations into leads by transdisciplinary
exploratory studies for translation into drug candidates or formulations
through robust preclinical and clinical research (Takenaka, 2001). In this
process, ‘safety’ remains the most important starting point and efficacy
becomes a matter of validation. The novelty of this approach is the
combination of living traditional knowledge such as that of ayurvedic,
African or Amerindian origin and the application of modern technology and
processes to provide better and safer leads (Patwardhan and Vaidya,
2010).
A good example that has emanated from ayurvedic medicine is the
treatment of psoriasis. Psoriasis is one of the most common
dermatological diseases, affecting approximately 2% of the world
population with no preventive or curative therapy. Using the reverse
pharmacological approach, the botanical drug product Desoris, which is an
extract of a single plant that effectively modulates cellular function, has
led to an improvement in psoriatic lesions. This product is being
developed to conform to US Food and Drug Administration (FDA)
guidelines for botanical drug products. It is now undergoing Phase 3
clinical trials in India (Vaidya and Devasagayam, 2007).
Increasingly, it is being proposed that drug discovery need not always be
confined to the discovery of a single molecule. Many analysts believe that
the current ‘one drug fits all’ approach may be unsustainable in the future.
In the management of polygenic syndromes and conditions, there is a
renewed interest in multi-ingredient synergistic formulations. Rationally
designed polyherbal formulation is being developed as option for multitarget therapeutic and prophylactic applications. This has led to the
development of standardized, synergistic, safe and effective traditional
herbal formulations with robust scientific evidence that can also offer
faster and more economical alternatives.
This approach is being used successfully in Tanzania with the Tanga AIDS
Working Group (TAWG) and where indigenous knowledge is being used to
alleviate suffering from HIV/AIDS (McMillen and Scheinman, 1999). This
group has treated over 4000 AIDS patients with herbs prescribed from
local healers. This impact has been most significant in reducing
opportunistic diseases accompanying HIV infection. These experiences are
important in scientific and rational drug discovery process. A crucial
challenge is to lever local and global knowledge systems effectively to
resolve development challenges (Patwardhan and Mashelkar, 2009).
Finally, drug discovery and development is known to be an extremely
complex technology- and capital-intensive process that is facing major
challenges with the current target-rich: lead-poor situation. One of the
major causes of attrition in drug discovery has been toxicity in human
trials and it is also recognized that drugs with novel mechanisms have
higher attrition rates. Better validated preclinical targets with proof-ofconcept of better efficacy and safety of drugs can mitigate such attrition
risks. This is where the reverse pharmacology approach, based on
traditional knowledge, can be useful and help reduce failure rates.
Drug discovery strategies based on natural products and traditional
medicines are re-emerging as attractive options. It is also being
recognized that drug discovery and development need not always be
confined to new molecular entities but that rationally designed, carefully
standardized, synergistic traditional herbal formulations and botanical
drug products with robust scientific evidence can also be alternatives.
Herein lie opportunities for the scientific community to add value to
indigenous biological resources within an enabling policy framework which
promotes and supports innovation.
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