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386 STUDENTBMJ | VOLUME 13 | OCTOBER 2005
I
t seems strange, when we have
many advanced chemical com-
pounds, to look for therapeutic
resources in rainforests. But mod-
ern medicine relies on natural
products, which make up more than
half of all drugs in industrialised
countries.
1
Theres still a lot to be
explored in the 7 800 000 km
2
Ama-
zon region, which is home to as
many as 80 000 plant species. Brazil-
ian flora comprise more than 20% of
the known species worldwide, and
the Portuguese described their use in
the management of disease as early
as 1500.
2
Phytopharmaceuticals and
phytotherapeutics
Basic concepts
Plant pharmacology has a specific
terminology of its own. Phytophar-
maceuticals is the name given to the
active principles extracted from
plants used by the drug industry in a
technologically processed way, such
as digoxin, escopolamine, or mor-
phine. Phytotherapeutics include a
range of plant based pharmaceutical
agents which vary widely in quality
and are made from modified plants
that have therapeutic properties but
were not previously purified. Accord-
ing to the World Health Organiza-
tion, these products have been
through some sort of pharmacologi-
cal or toxicological modification.
Thousands of plants are currently
used for therapeutic purposes, but
few have been transformed into phy-
totherapeutics, such as the spas-
molytic and anti-inflammatory
activity of Matricana chamomilla, and
the laxative formulations from Cassia
sena, Ginkgo biloba, Allium sativum
(garlic), and Calendula officinalis (cal-
endula).
1
An increasingly popular option
Around the world, people are
increasingly mixing elements of local
and biomedical tradition. In develop-
ing countries, medicinal plants are
used extensively by local care givers,
mainly because of their low cost and
the difficulties in seeing a doctor. In
Brazil, 60% of all processed drugs are
consumed by 23% of the population,
and 84% of all drugs are imported.
Local pharmaceutical companies are
not able to compete with the adver-
tising power of foreign companies. In
addition, government taxes are usu-
ally attractive to companies from
overseas. The low income of the pop-
ulation and the high costs of drugs
also contribute to this awful picture.
2 3
There is a shortage of studies of new
therapeutic agentsfewer than 2% of
Amazon higher plant species have
been tested for pharmacological
activity.
4
One way of reducing drug
imports, or even making drugs avail-
able at a lower cost, would be culti-
vating locally species that are known
to have therapeutic compounds.
Lack of evidence
There have been few scientific studies
on the efficacy and safety of phyto-
therapeutics. In Brazil, the require-
ment of preclinical and clinical tests
for registration was established in
1995, and the manufacturers of prod-
ucts already on the market had 10
years to assess and confirm their effi-
cacy.
2
These trials were supposed to
be carried out with local universities,
but few institutions got involved.
Since government inspection agen-
cies are unable to assess whether
manufacturers are complying with
the legislation, examples of products
taken off the market are unheard of.
2
The European Union accepts such
products on the basis of well docu-
mented minimal quality criteria
established by the WHO.
5
There is
also the mistaken view that phyto-
pharmaceuticals are harmless to the
body because they come from
nature. These agents have biologi-
cally active components which have
the same pharmacodynamic princi-
ples as any other agent.
How new drugs are
discovered
Methods of identification
Species with the largest therapeutic
potential can be identified by differ-
ent methods. One way is to look for
information on the traditional use of
the plants. That is the way we pro-
ceed here at our laboratory, explains
Dr Graa Brando from the pharma-
cognosy laboratory of the Faculty of
Pharmacy of the Federal University
of Minas Gerais, Brazil. We study
plants used in Brazilian traditional
medicine to treat malaria, diabetes,
and hypertension.
Another method is to study vari-
ous species of the same botanical
genus or family of already known
phytotherapeutics. After the screen-
ing stage, the material is collected,
identified, dehydrated, and its chemi-
cal components extracted. It is then
possible to purify those components
and to identify the compounds which
are pharmacologically active. The
pharmacological effects may be iden-
tified by tests performed in-vitro or
in-vivo.
Clinical studies
After its pharmacological activity
has been established, the product is
evaluated in clinical trials. Hundreds
of plants undergo some type of in-
vitro study. Roughly one third are
evaluated in-vivo, but few plants go
through clinical assessment, accord-
ing to Professor Brando. One of
the difficulties in doing research
with natural products is the high
cost.
Box 1 shows the strategies used in
in-vitro screening. These methods
are preferred by the screening pro-
grammes of drug companies.
1
Ethnopharmacology
Although plants can be collected
randomly or included in a chemo-
taxonomic classificationone incor-
porating botanical genus and species
sharing common characteristics, thus
possibly grouping plants with similar
therapeutic potentialregional folk-
lore may reveal useful clues and
guide appropriate studies.
Another strategy is to consider
how different cultures use the drugs.
The scientific exploration of biologi-
cally active agents in traditional usage
is known as ethnopharmacology.
This method has shown better results
than searching for new treatments by
chance.
1 6 7
The ethnopharmacologi-
cal approach depends on consider-
ing cultural diversity as biodiversity,
since the approach relies heavily on
traditional knowledge within
ethnic groups.
Amazon rainforest:
biodiversity and
biopiracy
The Amazon rainforest is home to a flora
with an enormous and vastly unexplored
pharmacological potential. Klaus Morales
and Tulio Vinicius investigate why
biopiracy is becoming a threat to Brazilian
biodiversity
G Shotgun approach: screens for
active substances regardless of
the drugs application
G Target directed approach: used
when a specific biological
action is desired
Drug strategies
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387 studentbmj.com
Resources of the Amazon
forest
Commonly used plants
Many plants sold at markets are
known locally as general tonics,
nerve tonics, or aphrodisiacs.
Researchers hypothesise potential
links between these agents and cen-
tral nervous system effects.
1
A nerve
tonic, Chaunochiton kappleri, showed
antidepressive-like effects in a num-
ber of psychopharmacological evalu-
ations.
1
A well known example of a
drug extracted from the Brazilian
biodiversity is the antihypertensive
agent captopril. This medicine was
developed from the poison of
Bothrops jararaca, a Brazilian snake.
Other examples of products
extracted not only from Amazon
plants but from other Brazilian
ecosystems are curare (Chondonden-
dron platyphyllummuscle relaxing
action), pilocarpine (Pilocarpus micro-
phyllusanti-glaucoma agent), and
quinine (Cinchona ledgerianaanti-
malarial). All these products are
exported from Brazil to a variety of
countries, where they are widely
used.
Box 2 lists some plants whose
pharmacological activity is already
known.
Plants under study
A variety of medicinal plants are cur-
rently being studied in Brazil and
other parts of the world. Many
already show promising results, such
as the Brazilian ginseng (Pfaffia panic-
ulata) as a neoplasic inhibitor
8 9
and
cats claw (Tomentosa uncaria) as an
antioxidant and anti-inflammatory
agent.
10
Despite the positive results,
the challenge remains, especially in
Brazil, to transform these products
into drugs. Ayahuasca shows promise
for the treatment of alcoholism and
substance abuse, serotoninergic
deficits, and immune modulation,
although studies under controlled
protocols such as the Food and Drug
Administration are still to be con-
ducted.
11
It is an aqueous preparation
made from a variety of plants, based
on Banisteriopsis caapi and Psycotria
viridis (hallucinogens). Both have a
high concentration of alkaloids, such
as N,N-dimetiltriptamine and others
from the -carbolin group, respec-
tively. The action of the drink can
therefore be attributed to the pres-
ence of these substances and not to
the rituals associated with it.
Drug companies
The potential of biodiversity has
attracted the attention of drug com-
panies, which aim to seek and extract
biological resources. The Amazon
basin is still the largest intact tropical
forest left in the world, but that seems
to be changing. Deforestation is
transforming forests which are rich in
species into biotically impoverished
regrowth forests.
Biopiracy
Many Brazilian plants have been col-
lected without the participation of
Brazilian researchers. They were
patented outside Brazil and are now
used commercially worldwide,
including in Brazil. This practice is
known as biopiracy, which is the
extraction of biological resources
from national territory without the
knowledge of local authorities. In
1992, Rio de Janeiro hosted ECO-92,
the United Nations Conference on
Environment and Development,
which was set to elaborate strategies
for implementing sustainable devel-
opment. Surprisingly, in that event
the Convention of Biological Diver-
sity was signed and established the
equal partition of benefits from the
commercial exploration of natural
products. It was expected to comple-
ment existing international arrange-
ments for the conservation of
biological diversity and sustainable
use of its components. Among other
objectives, it also aimed to conserve
and promote the sustainable use of
biological diversity for the benefit of
present and future generations.
12
Although biopiracy and plant traf-
ficking may be confused as syn-
onyms, these terms have distinct
meanings. Plant trafficking is the
action of collecting, capturing, or
transporting biological material,
regardless of its origin. Biopiracy,
however, is the identification, isola-
tion, or usage of genetic information
for the purpose of bioprospection,
said Christiane Duarte, environmen-
tal analyst of IBAMA, a governmen-
tal institution which deals with
environment protection, in a recent
issue of the regional scientific maga-
zine Minas Faz Cincia.
12
Nowadays,
transporting genetic material is quite
simple: a leaf is simply put in the
pocket, a plant seed is swallowed and
transferred to any place in the
world, Ms Duarte adds. Biopiracy in
itself does not have a direct environ-
mental impact. However, natives liv-
ing in forests are thus prevented
from using their products in a sus-
tainable way.
13
This happens when
products are patented and commer-
cialised for companies from other
countries.
Plants might be the source of new,
revolutionary drugs, but the rain-
forests which harbour them are still
threatened by uncontrolled and irra-
tional exploration.
Klaus Morales dos Santos fifth year medical
student, Tulio Vinicius de Oliveira Campos
fifth year medical student, Federal University of
Minas Gerais, Belo Horizonte/MG, Brazil
klausmorales@medicina.ufmg.br
We thank Dr Graa Lins Brando for her
contribution to this article.
1 Elisabetsky E, Shanley P. Ethnopharmacology
in the Brazilian Amazon. Pharmac Ther
1994;64:201-14.
2 Petrovick PR, Marques LC, De Paula IC. New
rules for phytopharmaceutical drug
registration in Brazil. J Ethnopharmacol
1999;66:51-5.
3 Wayland C. The failure of pharmaceuticals and
the power of plants: medicinal discourse as a
critique of modernity in the Amazon. Soc Sci
Med 2004;58:2409-19.
4 Gottlieb OR, Kaplan MAC. Amazon: chemical
treasure to be preserved. Cincia Hoje
1990;6:44-50.
5 World Health Organization. Guidelines for the
assessment of herbal medicines. Geneva: WHO,
1991.
6 Balick MJ. Ethnobotany and the identification
of therapeutic agents from the rainforest. In:
Chadwick DJ, Marsh J. CIBA Foundation
symposium on bioactive compounds from
plants. Bangkok, Thailand, 20-22 February,
1990;154:22-39.
7 Vlietinck AJ, Van Der Berghe DA. Can
ethnopharmacology contribute to the
development of antimalarial agents? J
Ethnopharmacol 1991;32: 141-54.
8 Matsuzaki P, Haraguchi M, Akisue G, Oloris
SC, Nagamine MK, da Silva TC Antineoplastic
effects of butanolic residue of Pfaffia
paniculata. Cancer Lett 2005. Published online
25 Jul doi:10.1016/j.canlet.2005.06.020.
9 Da Silva TC, Paula da Silva A, Akisue G, Luis
Avanzo J, Kazumi Nagamine M, Fukumasu H,
et al. Inhibitory effects of Pfaffia paniculata
(Brazilian ginseng) on preneoplastic and
neoplastic lesions in a mouse
hepatocarcinogenesis model. Cancer Lett
2005;226:107-13.
10 Cisneros FJ, Jayo M, Niedziela L. An Uncaria
tomentosa (cats claw) extract protects mice
against ozone-induced lung inflammation. J
Ethnopharmacol 2005;96:355-64.
11 McKenna DJ. Clinical investigations of the
therapeutic potential of ayahuasca: rationale
and regulatory challenges. Pharmacol Ther
2004;102:111-29.
12 Biopirataria. Minas Faz Cincia 2004;(Dec-
Feb):6-11.
13 Verma IM. Biopiracy: distrust widens the rich-
poor divide. Molec Ther 2002;5:95.
G Acanthusperun australa Cruzantimalarial
G Anacardium occidentalis L and Copaifera sp L
anti-inflammatory
G Bauhinia fortificataantidiabetic
G Casearia sylvestrisantiulcer
G Psychotria colorata and Dorstenia asaroides
analgesic
Box 2: Brazilian medicinal plants that
have undergone pharmacological
testing
Cinchona
ledgerianaor
quinine, a raw
material for gin
and tonic.
Apparently also
cures malaria
Plants might
be the source
of new,
revolutionary
drugs, but
they are still
threatened by
uncontrolled
and irrational
exploration
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