Content uploaded by Angelita Duarte Corrêa
Author content
All content in this area was uploaded by Angelita Duarte Corrêa on Apr 20, 2015
Content may be subject to copyright.
Journal of Medicinal Plants Research Vol. 4(22), pp. 2305-2312, 18 November, 2010
Available online at http://www.academicjournals.org/JMPR
DOI: 10.5897/JMPR10.572
ISSN 1996-0875 ©2010 Academic Journals
Review
Hoodia gordonii in the treatment of obesity: A review
Chrystian Araújo Pereira*, Luciana Lopes Silva Pereira and Angelita Duarte Corrêa
Departamento de Química, Laboratório de Bioquímica, Universidade Federal de Lavras – UFLA/MG, Campus
Universitário, Caixa Postal 3037, Cep: 37200-000, Lavras, MG, Brasil.
Accepted 27 september, 2010
According to data from the World Health Organization (WHO), one billion adults that are approximately
overweight currently exist in the world, of which three hundred million are obese. These numbers led to
the finding that obesity appears as a major global epidemic, affecting countries in all stages of
development. In Brazil, about 13% of the population is now considered obese and estimates suggest
that by the year 2025, the country will be fifth in the world in obesity ranking. Although some herbal
medicines are recommended in the treatment, numerous natural products are used indiscriminately to
prevent, reduce or delay weight gain; there are no studies of its therapeutic efficacy and safety. Among
these stands out the Hoodia gordonii commercial powder, a native plant of Africa, with purported
appetite inhibitory action attributed to the active glycoside P57, which was sold freely until its ban by
the Brazilian National Sanitary Surveillance Agency (ANVISA) in February 2007 because of the absence
of scientific proofs of its efficacy and safety. In addition, information on its mechanism of action in
inhibiting appetite and thirst are scarce, and its possible relation with leptin and insulin involved in the
neuroendocrine regulation of appetite and satiety.
Key words: Hoodia gordonii, obesity, herbal medicine, treatment.
INTRODUCTION
According to data from the World Health Organization
(WHO, 2010), one billion adults that are approximately
overweight currently exist in the world, of which three
hundred million are obese. These numbers led to the
finding that obesity appears as a major global epidemic,
affecting countries in all stages of development. In Brazil,
about 13% of the population is now considered obese
and estimates suggest that by the year 2025, the country
will be fifth in the world in obesity ranking (Brasil, 2009;
Ogden et al., 2006).
Considering that obesity is a multifactorial disorder, that
is, several factors are involved in their occurrence
including cultural, genetic, psychological, metabolic,
endocrine and environmental factors. Treatment and
therapeutic approach should also be performed by a
multidisciplinary staff.
Although some herbal medicines are usually
recommended for the treatment, numerous natural
products are used indiscriminately to prevent, reduce or
delay weight gain; there are no studies of its therapeutic
*Corresponding author. E-mail: capfarma@yahoo.com.br. Tel:
35 3829-1893 ou 35 9106-4442.
efficacy and safety. Among these stands out the Hoodia
gordonii (Apocinaceae, sub-family Asclepiadaceae)
powder, a plant native to Africa, with purported appetite
inhibitory action attributed to the active glycoside P57,
which was sold freely until its ban by the National
Sanitary Surveillance Agency (ANVISA) in 2007 because
of the absence of scientific proofs of its efficacy and
safety (Anvisa, 2007). In recent years, there has been a
growing interest in the plan reflected in the rising of
numerous commercial products based on H. gordonii in
different presentations. However, the binomial supply or
demand has created an unbalanced situation due to its
limited availability in relation to the large consumption of
the plant, causing the worrying possibility of tampering,
especially the cactus Opuntia ficus, popularly known as
cactus.
So far, there are no scientific studies related to the
chemical constituents (nutrients and anti-nutrients)
present in the H. gordonii commercial powder, as well as
its efficacy and toxicity. Further investigations are needed
on its mechanism of action in inhibiting appetite and
thirst, and their possible relationship with the hormones
insulin and leptin involved in regulating appetite and
satiety.
2306 J. Med. Plant. Res.
LITERATURE REVIEW
Obesity
Concept
Obesity is characterized by excessive accumulation of
body fat. For diagnosis in adults, the most commonly
used parameter is the body mass index (BMI). BMI is
calculated by dividing body weight by their squared
height. It is the standard used by the World Health
Organization (WHO) (WHO, 2010), which identifies
normal weight when the result of calculating the BMI is
between 18.5 and 24.9. To be considered obese, the BMI
should be above 30 (Abeso, 2010; Sbem, 2010; WHO,
2010).
Thus, overweight and obesity in the population are
currently defined as "a weight that is above what is
considered healthy for a specific height" (CDC, 2010),
using the various anthropometric parameters available for
evaluation.
Etiology
There are many causes of obesity. The excess weight
may be linked to the genetic heritage of the person, bad
eating habits or, for instance, the endocrine disorders
(Sbem, 2010). Considering that the genetic heritage of
human kind cannot have undergone major changes
during interval of a few decades, certainly environmental
factors must explain this epidemic. When evaluating a
clinically obese patient, however, one should consider
that several predisposing genetic factors may be playing
a significant role in determining energy imbalance of
overweight (Coutinho, 2007).
Moreover, it is known today from the investigation of
physiology and the neuroendocrine regulation of appetite
and satiety that the obesity epidemic is a result of the
combination of racial factors, genetic and cultural
environment by creating the so-called obesogenic
environment (Apovian, 2010).
Prevalence and progression
Obesity has reached epidemic proportions globally, with
more than one billion adults that are overweight, of which
300 million are clinically obese. Obesity rates have tripled
compared with 1980 data, collected in the countries of
North America, UK, Eastern Europe, Middle East, Pacific
Islands, Australia and China. However, the increase in
those rates is faster in developing countries than in the
developed countries (Opas/OMS, 2003).
In the last research conducted in the U.S., the National
Health and Nutrition Examination Survey (NHANES)
showed that rates of obesity among adults are 32.2% in
men and 35.5% in women (Flegal et al.,
2010). Studies present the United States as the country
of the highest rates of obesity among the population
(Fabricatore et al., 2008; Houston et al., 2008; Ogden et
al., 2006), however, recent data suggest that other
countries have already exceeded U.S. rates, like China
among children, and Australia and the UK among women
(Popkin, 2010).
Brazil has about 18 million people considered obese.
Adding the total number of overweight individuals, the
amount increases to 70 million, which is double
compared to three decades ago (Sbem, 2010).
Recent data show currently that in Brazil; approxi-
mately 13% of adults are obese, with the highest rates
among women (13.6%) than men (12.4%). These data
show great concern since the first assessment in 2006
show growth rates for each year (Brasil, 2009).
Problems associated
Obesity and overweight produce adverse metabolic
effects on blood pressure, cholesterol levels and blood
triglycerides and insulin resistance. Health problems are
not fatal, but extremely debilitating. WHO report in 2002
estimated that all over the world, 2.5 million people die
each year due to overweight (Opas/OMS, 2003).
Obesity is linked to some of the most prevalent
diseases in modern society, with greater risk associated
with development of diabetes mellitus. Furthermore, the
mortality risk increases even more for obese people who
are smokers (Francischi et al., 2000). Other medical
conditions such as biliary diseases, osteoarthritis, heart
disease and some cancers also have relationship with
obesity (Bray, 2004; Thande et al., 2008).
Economic impacts
Obesity accounts for 2 to 7% of the total cost of health
care in developing countries. The true costs of this
epidemic are undoubtedly much higher, since not all
disease associated with obesity is included in these
statistics (Opas/OMS, 2003).
Data show that in the United States in 1998, medical
expenses related to obesity including hospital patients or
outpatients and prescriptions, were approximately 78.5
billion dollars, estimating $147 billion in 2008 (Finkelstein
et al., 2009).
Brazil occupies the sixth place in the global ranking of
countries with problems of obesity. The direct costs
associated with this disease, including hospitalizations,
medical consultations and prescriptions reach 1.1 billion
dollars per year, equivalent to 12% of the total annual
expenses of Unified Health Services (SUS) with
hospitalizations (Gigante et al., 2009).
Treatments to reduce obesity
The treatments involve a balanced diet, physical exercise
often, drug therapy and behavioral change related to the
eating habits (Francischi et al., 2000). Suggestions for
reversal of the obesity epidemic include public health
campaigns, medical programs and community supported
by changes in food industry, aiming changes in eating
patterns and lifestyle. Community programs structured
physical activity, inside and outside of work can also
assist in a healthier lifestyle (Apovian, 2010).
Therapeutic options for these patients include various
agents promoting weight loss. The main study drugs are
sibutramine (serotonin reuptake inhibitor) and orlistat
(lipase inhibitor), catecholaminergic agents (or
amfepramone diethylpropion, fenproporex, mazindol and
ephedrine-caffeine combination), serotoninergic drugs
(fenfluramine, fluoxetine) and other drugs with some
action in weight loss (metformin, topiramate and
bupropion) (Halpern and Mancini, 2005).
Besides these, it is assumed that self-medication with
"natural products" slimming has increased considerably in
recent years because the population in general believes that
these drugs will not bring harm to health. The herbal drugs
used for reference are: artichoke (Cynara scolynmus), aloin
(Aloe vera), boldo (Peumus boldus), coot (Baccaharis sp),
cascara sagrada (Rhamnus purshiana), Centella asiatica,
citrin extract (Garcinia sp), chlorella (Chorella pyrenoidosa),
Maytenus (Maytenus ilicifolia), spirulina (Spirulina maxima),
Fucus sp. guarana (Paullinia cupana), false ginseng (Pfaffia
paniculata), glucomannan (Amorphophallus konjac)
jurubeba (Solanum paniculatum), passionflower (Passiflora
alata ) and senna (Cassia angustifolia) (Azeredo et al.,
2005). In addition, other products such as Hoodia gordonii
have been consumed for the same purpose, without
however, being scientific proof of its efficacy and safety.
Finally, the current perception of fat cell as an endocrine
organ, in addition to contributions from the intestine and
pancreas, helps us understand the origins of the
neuroendocrine regulation of appetite and satiety by
substances such as leptin, insulin and ghrelin, representing
a field of possibilities in the treatment of obesity (Apovian,
2010; Bays, 2004).
Hormones involved in neuroendocrine regulation of
appetite and satiety
Leptin
Leptin (Greek mites = thin) is a protein composed of 167
amino acids with a structure similar to cytokines and is
mainly produced in the adipose tissue which is
responsible for the control of food intake, acting in cells of
the hypothalamus in the central nervous system
(Reseland et al., 2001). The action of leptin in the
hypothalamus in mammals, promotes reducing food
intake and increase energy expenditure, in addition to
regulating neuroendocrine function and energy meta-
bolism (Auwerx and Staels, 1998; Friedman and Halaas,
1998).
Leptin reduces appetite from the inhibition of appetite-
related neuropeptides such as neuropeptide Y (NPY),
Pereira et al. 2307
and also stimulates the expression of anorexigenic
neuropeptides: hormone α-melanocyte-stimulating (α-
MSH), corticotropin-releasing hormone (CRH) and
substances synthesized in response to amphetamine and
cocaine (CART) (Elmquist et al., 1998; Friedman and
Halaas, 1998). Thus, high levels of leptin reduces food
intake while low levels induces hyperphagia (Romero and
Zanesco, 2006).
However, leptin blood levels increased much
(hyperleptinemia), found mainly in obese people, may
indicate a condition of leptin resistance state similar to
insulin resistance that occurs in diabetes mellitus. In this
condition, the high leptin levels are associated with
hyperphagia and obesity (Considini et al., 1996).
Studies with rats have shown that leptin activates a
potassium channel ATP-sensitive, indicating that this
channel may function as molecular target of the hormone
in hypothalamic neurons (Spanswick et al., 1997).
Insulin
Insulin is a protein composed of two chains (A and B)
with 21 amino acids in each, linked by two disulfide
bonds. The amino acid composition is variable for
different animals, but in each chain 10 residues are
common, and few essential for biological activity. The
insulin molecule exists as a monomer only at low
concentrations (<0.1 mM or ~ 0.6 mg/mL). Under
physiological conditions, insulin is normally maintained at
concentrations below 10 to 3 mM, to ensure their
circulation, and exerts its biological activity as a
monomeric molecule. For concentrations above 0.1 mM,
it occurs in insulin dimerization (Chien, 1996).
It is the most anabolic hormone known and essential to
the maintenance of glucose homeostasis, growth and
differentiation. Insulin regulates glucose homeostasis at
several levels, reducing its production by the liver (via
decreased gluconeogenesis and glycogenolysis) and
increasing capture peripheral, mainly in muscle and
adipose tissue. Insulin also stimulates lipogenesis in the
liver, adipocytes and reduces lipolysis, and increases the
synthesis and inhibits protein degradation (Carvalheira et
al., 2002).
Insulin produced by beta cells and its serum
concentration is also proportional to adiposidade
(Halpern et al., 2004). With its anabolic effect, insulin
increases glucose uptake, and the fall of blood glucose is
a stimulus for increased apetite (Woods et al., 1998). The
recent discovery receptors for insulin in the brain
demonstrated its essential function in the central nervous
system to stimulate satiety and energy expenditure, in
addition to regulating action of leptin (Hallschmid and
Schultes, 2009; Schwartz, 2000).
Ghrelin
Ghrelin (English grow = growth) is a gastrointestinal
2308 J. Med. Plant. Res.
hormone identified in the stomach of rats, which has as
one of its main functions the increased secretion of
growth hormone (GH) (Kojima et al., 1999; Kojima et al.,
2001). It is a peptide composed of 28 amino acids,
produced Gr predominantly by cells of the gastrointestinal
tract (Bednarek et al., 2000; Kojima et al., 1999).
Ghrelin is directly involved in regulating short term
energy balance and is one of the most important flags to
the top of food intake. Its concentration remains high
during periods of fasting and periods prior to meals,
falling immediately after feeding, which suggests a neural
control. Besides increasing the appetite, it also stimulates
the digestive secretions and gastric motility (Konturek et
al., 2004; Nakazato et al., 2001).
Animal studies indicate that leptin signaling plays an
important role in the hypothalamic centers that regulate
food intake and adiposity, suggesting its participation in
stimulus to start a meal (Nakazato et al., 2001; Romero
and Zanesco, 2006).
The plasma concentration of ghrelin decreases after
meals rich in carbohydrates, while the elevation of insulin,
however, increased levels are found after meals rich in
animal protein and lipids, accompanied by mild insulin
increase (Erdmann et al., 2004; Salbe et al., 2004).
Hoodia gordonii (Apocinaceae)
Taxonomic information
Hoodia is a plant of the order of Gentianales, family of
Apocinaceae, sub-family of Asclepiadaceae. This family
consists mainly of medicinal plants (herbs) and shrubs
with white sap, comprising about 250 genera and 2000
species, some of which possess succulent stems and
thorns, similar to cacti with leaves pequenas (University
of Hawaii, 2007; Van Heerden, 2008). The genus Hoodia
has several species, especially H. gordonii, H.pilífera, H.
lugardii and H. ruschii main research subjects (Archer
and Victor, 2003; Chow et al., 2005; MacLean and Luo,
2004).
In common with other species of the genus, Hoodia
gordonii is succulent and fleshy, with several erect and
cylindrical rods varying in color from gray-green to gray-
brown and flower-shaped crown with about 100 mm. The
tubers are prominent, fused in their lower halves of stems
11 to 17 at obtuse angles, and each end of a very sharp
thorn 6 to 12 mm (Bruyns, 2005).Due to their prickly
appearance, the plant H. gordonii is often referred to as
"cactus" or "cactus of the desert" by the press, although
in reality, it cannot be characterized as a true cactus that
belongs to the family Cactaceae (Van Heerden, 2008).
There are currently 13 species (H. alstonii, H. currorii,
H. Dreger, H. flava, H. gordonii, H. juttae, H.
mossamedensis, H. officinalis, H. parviflora, H.
pedicellata, H. pilifera, H . ruschii, and H. triebneri) and
H.gordonii which are of primary interest because of their
anorectic properties (Avula et al., 2007; Van Heerden et
al., 2007).
Distribution
The Hoodia plant is native to Africa, being found in the
deserts of Namibia and the Kalahari. The species Hoodia
gordonii (Figure 1) is grown mainly in South Africa,
Namibia, Botswana and Angola, by the San people, a
tribe whose indigenous inhabitants are known as
Bushmen. These Indians call the plant xhoba (WHO,
2003).
In South Africa, Hoodia species are protected, and
permits are required by official bodies for the collection,
cultivation, transportation or export of plants. They are
related to plant slow-growing, and difficult to culture. Its
limited number available cannot sustain a strong market,
which in future will depend on plants grown for the
marketing purposes (Van Heerden, 2008).
Currently, H. gordonii is listed as a species at risk of
extinction and its export is tightly controlled by the South
African government and by international agreements to
protect plant species (Avula et al., 2008).
History
For thousands of years, the San people, one of the oldest
habitants of southern Africa, took pieces of H. gordonii
bitten during the hunt. For several days of hunting without
food and water, they ingested the plant just to satisfy
hunger, inhibit appetite and keep the provision (WHO,
2003). Apparently, the plant sap relieves the sensation of
hunger during long trips in search of indigenous hunting
(Bruyns, 2005).
This effect of suppression of appetite aroused scientific
interest and in the 60s of the twentieth century, the
Council for Scientific and Industrial Research (CSIR),
located in South Africa, isolated and patented an appetite
suppressing molecule present in H. gordonii, called P57.
Later in 1997, the CSIR licensed the rights to the
molecule P57 British Company Phytopharm. After initial
tests, the drug seemed promising and part of Phytopharm
sold the rights to Pfizer pharmaceutical industry for
21million dollars. The companies expected the drug to
revolutionize the market for slimming products which
moved about 9.5 billion dollars at the time. However, a
protest international companies was accused of biopiracy
and began a long legal battle between business and the
CSIR on one side and San people on the other; the
division of profits from the exploitation and marketing of
Hoodia (WHO, 2003).
In 2002, Pfizer released the rights to the Hoodia,
claiming that the development of the P57 had been
suspended because of difficulty in their synthesis and
evidence of side effects in mice, caused by other
Pereira et al. 2309
Figure 1. Hoodia gordonii (Hübner. and Tränkle, 2004).
components of the extract could not be easily removed
(Bindra, 2005). According to Jasjit Bindra, head of
research for hoodia at Pfizer, "surely, Hoodia has a long
way to go before it can receive the approval of the North
American Food and Drug Administration (FDA). Until
safer formulations are developed, people Interested in
the diet should avoid its use. "
Finally in March 2003, after years of negotiation, an
agreement was reached between the parties. Under
terms of the agreement, the CSIR will pass to the San
people, 8% of all payments received from licensing to
Phytopharm, and 6% of all royalties that the CSIR
receives on drug will be commercially available. It is
hoped that in future, the transfer will be 10 to 12 million
dollars per year (WHO, 2006).
Today the great interest in the inhibitory properties of
Hoodia appetite, gives an intense demand for products
based on the plant. It is estimated that only in the U.S.
market are available for marketing products in over 100
different presentations (tablets, capsules, gels, juices,
powders, teas, and others) which contain the plant in its
composition (Avula et al., 2008). So the high demand in
contrast to the scarce supply have created a scenario in
which the adulteration of products for other species such
as O. ficus and even other species of the genus Hoodia
has become a real possibility (Avula et al., 2007; Avula et
al., 2008; Rader et al., 2007; Van Heerden, 2008).
Chemical composition of the extracts of Hoodia
Various active components were isolated by researchers
from CSIR and have been revealed in recent patents
(Bronner, 2005; Gardiner et al., 2006; MacLean, 2006;
Raskin et al., 2006; Rifkin, 2005; Van Heerden et al.,
2004; Verdegem et al., 2008). However, the supposed
active component present in extracts from H. gordonii is a
steroidal glycoside trirabinosídeo, 14-OH, 12-
tigloilpregnano (MW = 1008), known as P57 (Figure 2),
responsible for appetite suppressing (MacLean and Luo,
2004).
The putative active component in extracts of H.
gordonii is a trirhabinoside, 14-OH, 12-tigloyl pregnane
steroidal glycoside (MW = 1008). The core steroid,
particularly regarding the 14-OH substitution, is
somewhat similar to other cardenolides (MacLean and
Luo, 2004). The 14-glucoside is not unique to H. gordonii,
which is also found in other species of the genus as
H.currori, H.macranth, H.parviflora, and H. H.pilifera
ruschii (Avula et al., 2007; Avula et al., 2008; Van
Heerden et al., 2007).
Recently, ten new derivatives C (21)-steroid, called
gordonisides were isolated from chloroform extracts
obtained from aerial H. gordonii. The new compounds
were based on 3-beta, 14-beta-hydroxy-pregn-5-en-17-
.22 betaona (Dall'acqua and Innocenti, 2007).
2310 J. Med. Plant. Res.
Figure 2. Structure of glicosyde P57. Steroidal glycoside trirabinosíde,
14-OH, 12-tigloilpregnane (Janssen et al., 2008).
Also, shoot were isolated on eleven new
oxipregnanos, glucosides with the basic structure 12-O-
beta-called tigloil isoramanona hoodigosides. Their
structures were determined by chemical evidence and
magnetic resonance nuclear (Pawar et al., 2007).
Information regarding the chemical composition
(proteins, carbohydrates, lipids, vitamins, fiber, poly-
phenols, nitrate, oxalic acid, lectins, saponins and
digestive enzyme inhibitors) which may be present in H.
gordonii, are scarce and sometimes non-existent.
Pharmacological effects of extracts of Hoodia
gordonii
Long-term biological assays not published by
companies Phytopharm and Pfizer, with extracts of the
dried sap of the plant, which contained not only P57 but
also multiple components, were conducted with obese
diabetic Zucker rats. The results showed anorexic
activity and reversal of diabetes, maintained during the
administration of doses. Other tests reveals that the
inhibition of feeding and weight loss are independent of
the nutrient content of the diet and also occur in overfed
animals with a highly palatable diet (MacLean and Luo,
2004). In addition, Phytopharm announced short-term
studies in humans, during which the extract of H.
gordonii was well tolerated (MacLean and Luo, 2004).
Trichoplusia ni larvae fed a diet containing latex of H.
gordonii (1,000 ppm) showed no inhibition of growth
and reproduction remained unchanged as compared to
larvae treated with control diet (Chow et al., 2005).
Intracerebroventricular injections of steroidal glycoside
P57AS3 (P57), isolated and purified extracts of H.
gordonii in rats showed that the compound has a likely
mechanism of action in the central nervous system. The
results showed that the compound increased the
content of ATP in hypothalamic neurons by up to
150%, and within 24 h, reduction of food intake by 60%
(MacLean and Luo, 2004).
Works using rats demonstrated that treatment with
purified extracts of H. gordonii containing active
glycosides in the diet or administered by gavage were
effective in reducing weight (Tulp et al., 2001; Tulp et
al., 2002; Van Heerden et al., 2007).
Studies with mammals including humans have shown
that the compound P57 was able to reduce gastric acid
secretion, allowing its use in formulations for treatment
of disorders and diseases related to excessive gastric
secretion (Hakkinen et al., 2004). Moreover,
supplementation of the diet of broiler chickens with
powdered H. gordonii at concentrations 000 to 500 mg/
animal / day, showed no change in food consumption
during 30 days of experiment (Mohlapo et al., 2009).
Accordingly, Holt (2006) formulations containing H.
gordonii and other herbal medicines are able to control
obesity and suppress appetite, and aid in the treatment
of metabolic disorders associated with obesity. The San
people for thousands of years consumed H. gordonii
due to the supposed effects of inhibition of hunger and
thirst (WHO, 2006).
Scientific research
Despite the great commercial interest by H. gordonii, as
evidenced by the large consumption in the form of
capsules, there are few reports about the plant. Some
sought to elucidate the components ativos (Pawar et al.,
2007; Shukla et al., 2009), while others devoted
themselves to understanding the mechanism of appetite
suppression (Dall'acqua and Innocenti, 2007; MacLean
and Luo, 2004).
Currently, due to the high possibility of fraud and
adulteration of products marketed as H. gordonii, most
studies are aimed at developing analytical
methods, mainly using high performance liquid
chromatography for identification of glycosides
characteristic and confirm the authenticity of
commercial samples (Avula et al., 2006; Avula et al.,
2007; Avula et al., 2008; Janssen et al., 2008).
With regard to the side effects and chronic effects
from ingesting H. gordonii, there are no reports in the
literature. This fact led to the banning of advertising and
handling in Brazil by the Brazilian Sanitary Surveillance
Agency (ANVISA) in 2007 (Anvisa, 2007).
ACKNOWLEDGEMENTS
We thank CAPES for the doctoral scholarship and
FAPEMIG for the financial support to the project.
REFERENCES
Associação Brasileira Para O Estudo Da Obesidade E Da Síndrome
Metabólica (2010) Brazilian Association For The Study Of Obesity
And Metabolic Syndrome. Available at www.abeso.org.br. Access
in Feb 12.
Agência Nacional De Vigilância Sanitária/National Sanitary
Surveillance Agency (2007). Resolução RE 424 de 15 de fevereiro
de 2007. Dispõe sobre a proibição da manipulação e
comercialização, em todo o território nacional, da substância
Hoodia gordonii, como medida de segurança por não atender às
exigências regulamentares desta agência. Available at
www.anvisa.org.br. Access in March 25.
Apovian CM (2010). The causes, prevalence, and treatment of
obesity revisited in 2009: what have we learned so far? Am. J. Clin
Nutr. 91(suppl):277S–9S.
Archer RH, VIctor JE (2003). Hoodia pilifera subs pillansii,
Apocyanaceae: Asclepiadoideae. Curtis’s Botanical Magazine.
20(4):219-24.
Auwerx J, Staels B (1998). Leptin. Lancet. Nature. 351:737–42.
Avula B, Wang Y, Pawar RS, Shukla YJ, Khan I (2006). Determination
of the appetite suppressant P57 in Hoodia gordonii plant extracts
and dietary supplements by liquid chromatography/electrospray
ionization mass spectrometry (LC-MSD-TOF) and LC-UV methods.
J. AOAC Int. 89(3):606-11.
Avula B, W ang Y, Pawar RS, Shukla YJ, Khan IA (2007). Chemical
fingerprinting of Hoodia species and related genera: chemical
analysis of oxypregnane glycosides using high-performance liquid
chromatography with UV detection in Hoodia gordonii. J. AOAC
Int. 90(6):1526-531.
Avula B, Wang Y, Pawar RS, Shukla YJ, Smillie TJ, Khan IA (2008).
A rapid method for chemical fingerprint analysis of Hoodia species,
related genera and dietary supplements using UPLC-UV-MS. J. of
Pharm. Biomed Anal. 48:722-31.
Azeredo FS, Guimarães RI, Paula JR, Cunha LC (2005). Validação
de técnica analítica em cromatografia em camada delgada
comparativa para identificação de fármacos anorexígenos
sintéticos em produtos fitoterápicos. Infarma. 17:5-6.
Bays HE (2004). Current and investigational antiobesity agents and
obesity therapeutic treatment targets. Obes. Res. 12(8):1197-211.
Bednarek MA, Feigner SD, Pong SS, McKee KK, Hreniuk DL, Silva
MV (2000). Structure-function studies on the new growth hormone-
releasing peptide, ghrelin: minimal sequence of ghrelin necessary
for activation of growth hormone secretagogue receptor 1a. J.
Med. Chem. 43(23):4370-376.
Bindra, J (2005). A Popular Pill's Hidden Danger. New York Times,
New York, 26 abr.
Brasil. Ministério da Saúde (2009). 13% two Brazilians are obese
adults: given and trends, Brazil. Available at:
Pereira et al. 2311
<http://portal.saude.gov.br/portal/saude/default.cfm>. Access in:
Nov 10, 2009.
Bray GA (2004). Medical consequences of obesity. J. Clin.
Endocrinol. Metab. 89:2583–589.
Bronner JS (2005). Appetite-suppressing, lipase-inhibiting herbal
composition. United States Patent 20050276869.
http://www.freepatentsonline.com/20050276869.html
Bruyns PV (2005). Stapeliads of Southern Africa and Madagascar.
Umdaus Press, Pretoria, vol 1, pp. 4–8.
Carvalheira JBC, Zecchin HG, Saad MJA (2002). Ways of giving
insulin Signaling. Arq Bras Endocrinol Metab. 46(4):419-25.
CHIEN, YW (1996). Human insulin: Basic sciences to therapeutic
uses. Drug Dev. Ind. Pharm. 22:753-89.
CENTERS FOR DISEASE CONTROL AND PREVENTION (CDC)
USA (2010) Available at:
<http://www.cdc.gov/nccdphp/dnpa/obesity/defining.htm> Access in
jan, 10, 2010.
Chow JK, Akhtar Y, Isman MB (2005). The effects of larval
experience with a complex plant latex on subsequent feeding and
oviposition by the cabbage looper moth: Trichoplusia ni
(Lepidoptera: Noctuidae). Chemoecology. 15:129-33.
Considini RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW,
Nyce MR (1996). Serum immunoreactive leptin concentrations in
normal-weight and obese humans. N. Engl. J. Med. 334(5):292-95.
Coutinho W (2007); Etiologia da obesidade. Revista ABESO. 30.
Dall’Acqua S, Innocenti G (2007). Steroidal glyxosides from Hoodia
gordonii. Steroids.;72:559-68.
Elmquist JK, Maratos-Flier E, Saper CB, Flier JS (1998). Unraveling
the central nervous system pathways underlying responses to
leptin. Nat. Neurosci. 1:445–50.
Erdmann J, Topsch R, Lippl F, Gussmann P, Schusdziarra V (2004).
Postprandial response of plasma ghrelin levels to various test
meals in relation to food intake, plasma insulin, and glucose. J.
Clin. Endocrinol. Metabol. 89(6):3048-054.
Fabricatore AN, Wadden TA, Rohay, JM, Pillitteri, JL, Shiffman S,
Harkins AM, Burton SL (2008). Weight Loss Expectations and
Goals in a Population Sample of Overweight and Obese US Adults.
Obesity. 16:2445–450.
Finkelstein EA, Trogdon JG, .Cohen JW, Dietz W (2009). Annual
Medical Spending Attributable To Obesity: Payer-And Service-
Specific Estimates. Health Affairs. 28(5):w822-w831. Flegal KM,
Carroll MD, Ogden CL, Curtin LR (2010). Prevalence and Trends
in Obesity Among US Adults, 1999-2008. Journal of American
Medical Association (JAMA). 303(3):235-41.
Francischi RPP, Pereira LO, Freitas CS, Klopfer M, SANTOS RC,
VIEIRA P, Lancha Júnior AH (2000). Obesidade: atualização sobre
sua etiologia, morbidade e tratamento. Rev. Nutr. 13(1):17-28.
Friedman JM, Halaas JL (1998). Leptin and the regulation of body
weight in mammals. Nature, 395(22):763-70.
Gardiner Paul T, Heuer MA (2006). Diet supplement for causing rapid
weight loss, controlling appetite, managing stress, supporting
relaxation, combating fatigue and supporting mental well-being.
United States. 20060286183
http://www.freepatentsonline.com/20060286183.html
Gigante DP, Moura EC de, Sardinha LMV (2009). Prevalência de
excesso de peso e obesidade e fatores associados. Revista de
Saúde Pública. 43(supl.2):83-89.
Hakkinen J, Horak RM, Maharaj V (2004). Gastric Acid Secretion.
United States. 6808723B2. www.google.com/patents
Hallschmid M, Schultes B (2009). Central nervous insulin resistance:
a promising target in the treatment of metabolic and cognitive
disorders? Diabetologia. 52:2264–269.
Halpern ZSC, Rodrigues MDB, Costa RF (2004). Determinantes
fisiológicos do controle do peso e apetite. Revista de Psiquiatria
Clínica. 31(4):150-53.
Halpern A, Mancini MC (2005). Diabesity: Are Weight Loss
Medications Effective? Treatments in Endocrinology. 4(2):65-74.
Holt S (2006). Herbal compositions containing Hoodia. United States.
WO2006079055A1. www.wipo.org.
Houston DK, Cai J, Stevens J (2008). Overweight and Obesity in
Young and Middle Age and Early Retirement: The ARIC Study.
Obesity. 17:143–49.
2312 J. Med. Plant. Res.
Hübner F, Tränkle U (2004). Available at:
<http://www.asclepidarium.de/Fotoausstellung%20Bilder%20Hoodi
a.htm>. Access in May 21, 2010.
Janssen H, Swindells C, Gunning P, Wang W, Grün C, Mahabir K,
Maharaj VJ, Apps PJ (2008). Quantification of appetite
suppressing steroid glycosides from Hoodia gordonii in dried plant
material, purified extracts and food products using HPLC-UV and
HPLC–MS methods. Analytica Chimica Acta. 617:200–07.
Kojima M, Hosoda H, Date Y (1999). Ghrelin is a growth-hormone-
releasing acylated peptide from stomach. Nature. 402:656-60.
Kojima M, Hosoda H, Matsuo H, Kangawa K (2001). Ghrelin:
discovery of the natural endogenous ligand for the growth-hormone
secretagogue receptor. Trends Endocrinol. Metabol. 12(3):118-22.
Konturek SJ, Konturek JW, Pawlik T, Brzozowki T (2004). Brain-gut
axis and its role in the control of food intake. Journal of Physiology
and Pharmacology. 5:137-54.
MaClean DB, Luo L (2004). Increased ATP content/production in the
hypothalamus may be a signal for energy-sensing of satiety:
studies of the anorectic mechanism of a plant steroidal glycoside.
Brain Research.; 1020:1 –11.
MacLEAN, DB (2006). Modulation of ATP production or content in the
hypothalamus. United States Patent 20060233861
http://www.freepatentsonline.com/20060233861.html
Mohlapo TD, Ng’ambi JW, Norris D, Malatje MM (2009). Effect of
Hoodia gordonii meal supplementation at finisher stage on
productivity and carcass characteristics of Ross 308 broiler
chickens. Tropical Animal Health and Production. 41:1591–596.
Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K
(2001). A role for ghrelin in the central regulation of feeding.
Nature, 409(6817):194-98.
OGDEN CL, CARROLL MD, CURTIN LR (2006). Prevalence of
overweight and obesity in the United States, 1999–2004. JAMA.;
295:1549–555. ORGANIZAÇÃO PANAMERICANA DE SAÚDE
sobre alimentação saudável, atividade física e saúde. OPAS/OMS,
Brasília, 60p. www.who.int. Access in Jan 12.
Popkin BM (2010). Recent dynamics suggest selected countries
catching up to US obesity. American Journal of Clinical Nutrition.
91(suppl):284S–8S.
Pawar RS, Shukla YJ, Khan SI, Avula B (2007). New oxypregnane
glycosides from appetite suppressant herbal supplement Hoodia
gordonii. Steroids. 72(6-7):524-34.
Rader JI, Delmonte P, Trucksess MW (2007). Recent studies on
selected botanical dietary supplement ingredients. Anal Bioanal
Chem. 389:27–35.
RASKIN, ILYA; (Manalapan, NJ), O'NEAL,; JOSEPH M. III; 2006.
Appetite-suppressing compositions and methods. United States.
20060084638 http://www.freepatentsonline.com/20060084638.html
Reseland JE, Anderssen SA, Sovoll K, Hjermann I, Urdal P, Holme I
Et AL (2001). Effect of long-term changes in diet and exercise on
plasma leptin concentrations. American Journal of Clinical Nutrition.
73(2):240-45.
Rifkin CH (2005). Appetite satiation and hydration beverage. United
States.
20050276839.http://www.freepatentsonline.com/20050276839.html
Romero CEM, Zanesco A (2006). O papel dos hormônios leptina e
grelina na gênese da obesidade. Revista de Nutrição. 19(1):85-91.
Salbe AD, Tshop MH, Delparigi A, Venti C, Tataranni PA (2004).
Negative relationship between fasting plasma ghrelin
concentrations and ad libitum food intake. J. Clin. Endocrinol.
Metabol. 89(6):2951-956.
Schwartz MV (2000). Staying slim with insulin in mind. Science.
289:2066-067.
Shukla YJ, Pawar RS, Ding Y, LI X, Ferreira D, Khan IA (2009).
Pregnane glycosides from Hoodia gordonii. Phytochemistry.
70:675
SOCIEDADE BRASILEIRA DE ENDOCRINOLOGIA E
METABOLOGIA (SBEM) (2010). Available at:
www.endocrino.org.br. Access in Jan 15.
Spanswick D, Smith MA, Groppi VE, Logan SD, Ashford MLJ (1997).
Leptin inhibits hypothalamic neurons by activation of ATP-sensitive
potassium channels. Nature. 390(4):521-25.
Thande NK, Hurstak EE, Sciacca RE, Giardina EV (2008).
Management of Obesity: A Challenge for Medical Training and
Practice. Obesity. 17:107–13.
Tulp OL, Harbi NA, Mihalov J, Dermarderosian A (2001). Effect of
Hoodia plant on food intake and body weight in lean and obese LA/
Ntul//-cp rats. FASEB Journal. 15:A404.
Tulp OL, Harbi NA, Mihalov J, Dermarderosian A (2002). Effect of
Hoodia Plant on Weight Loss in Congenic ObeseLA/Ntul//-cp rats.
FASEB Journal.; 16(4):A654.
UNIVERSITY OF HAWAII. Available
at:<http://www.botany.hawaii.edu/faculty/carr/asclepiad.htm>.
Access Jul. 15 Jul, 2007.
Van Heerden FR, Vleggaar R, Horak R M, Learmonth RA, Maharaj V,
Whittal R D (2004). Use of extracts from Hoodia gordonii and
Hoodia lugardii for the preparation of a medicament for use in the
suppression of appetite. CSIR (ZA). EP1438965
http://www.freepatentsonline.com/EP1438965.html
Van Heerden FR (2010) Hoodia gordonii: A natural appetite
suppressant. Journal of Ethnopharmacology.119:434–37.
Van Heerden FR, Horak RM, Maharaj VJ, Vleggaar R, Senabe JV,
Gunning P J (2007). An appetite suppressant from Hoodia species.
Phytochemistry.68:2545–553.
Verdegem PJE, Hughes SF, Hedges C A, Bangerter PG (2008).
Method and composition for providing controlled delivery of
biologically active substances. United States Patent Application
20080305096 http://www.freepatentsonline.com/2008030509.html
Woods SC, Seeley RJ, Porte JR, SCHWARTZ DMW (1998). Signals
that regulate food intake and energy homeostasis. Science.
280:1378-383.
WORLD HEALTH ORGANIZATION – W HO (2006). Bulletin of the
World Health Organization. 84(5):345.
WORLD HEALTH ORGANIZATION – W HO (2003). Bulletin of the
World Health Organization. 81(5):382.ORGANIZAÇÃO MUNDIAL
DA SAÚDE (OMS) (2003). Available at: (OPAS)/ORGANIZAÇÃO
MUNDIAL DE SAÚDE (OMS) (2003). Doenças crônico-
degenerativas e obesidade: estratégia mundial