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Schweiz. Zschr. GanzheitsMedizin 2009;21(6):300–306. © Verlag für GanzheitsMedizin, Basel. www.ganzheitsmedizin.ch

Hoodia: A Herb Used in South African Traditional


Medicine – A Potential Cure for Overweight?
Pharmacognostic Review of History, Composition,
Health-Related Claims, Scientific Evidence and
Intellectual Property Rights
Sabine Glasl
Department of Pharmacognosy, University of Vienna, Vienna, Austria

T he succulent Hoodia has been used


by the San, indigenes from South-
ern Africa, for generations as an ap-
Background: Within the last decade, the crude drug Hoodia and preparations derived from Hoodia
[Hoodia gordonii (MASSON) SWEET ex DECNE] have become increasingly popular. These food
supplements – sold partly via the Internet – are promoted as appetite suppressants for weight
reduction. This succulent plant is consumed by South African natives, the San, to stop thirst and
petite suppressant and thirst quencher hunger during hunting. Objective: To review current knowledge on origin, chemical constituents,
during famine and low food supply [1]. ethnopharmacology and pharmacology of Hoodia. Historical development and intellectual proper-
From ancient times, the San have made ty rights are addressed as well. Method: Systematic analysis of the scientific literature on Hoodia
found in major electronic databases. Results: A considerable number of patents have been
use of the plant’s properties which al- deposited for hoodia, which is claimed to suppress appetite, develop antidiabetic activity and pro-
low them to endure long hunting ex- tective effects against gastric acid secretion. The originally planned development of Hoodia as a
peditions with fewer provisions [2]. pharmaceutical was abandoned in 2004, at which time Hoodia was classified as a functional food
This traditional knowledge has been and temporarily suspended by the end of 2008. Knowledge on its chemical composition focuses
on pregnane glycosides, one of which is regarded as the active principle. Analytical methods
kept among the indigenes and was which enable screening of the crude drug and formulations thereof have been devised. A huge
passed on from generation to genera- amount of food supplements claiming to contain Hoodia turned out to lack any of its pregnane
tion by word of mouth until the Coun- constituents and must be regarded as adulterations. Studies on the above-mentioned beneficial
health claims are scarce. The metabolic stability of the main steroidal glycoside and its interaction
cil for Scientific and Industrial Research
with drug-metabolizing enzymes were assessed in vitro. In vivo, Hoodia was shown to reduce
(CSIR) in South Africa became acquaint- caloric uptake and body weight after either intracerebroventricular injection or oral ingestion.
ed with this information. In the early However, neither clinical nor toxicity data have been published to date. Two cases of adverse
sixties, an investigation was launched reactions (anticholinergic syndrome, acute hepatitis) upon intake of Hoodia-containing prepara-
tions have been reported. Conclusion: Current knowledge on Hoodia and its products is incom-
at the CSIR to determine the nutritional
plete. The phytochemical profile needs to be studied in more detail for further classes of com-
value and also any possible long-term pounds besides the well-investigated pregnane glycosides. There are no reliable data on toxicity,
toxic effects of “food from the veld” [3]. safety and clinics. Moreover, the Hoodia issue is intrinsically tied to questions concerning the
More than 1000 species of wild South Convention of Biological Diversity and protection of species: The benefit-sharing agreements
signed with the San are to be respected and permits from the authorities are required for collec-
African plants – among them Hoodia tion, culture, transport or export because Hoodia is a protected plant.
species – known to be used as indige-
nous “bush foods” were screened [3]. Keywords: Hoodia, San, appetite suppression, safety, quality control, pharmacognosy
This research aimed to inform the
South African Defence Force about the
toxic and nutritional properties of wild Hoodia: Natürliche Heilkraft zur Gewichtsreduktion aus der Traditionellen
foods and so to ascertain their suit- Medizin Südafrikas? Ein Review zu Geschichte, Zusammensetzung, Wirk-
ability for the army [4]. As a result, the versprechen, wissenschaftlicher Evidenz und Fragen des geistigen Eigentums
CSIR patented the oxypregnane glyco- Hintergrund: Die pflanzliche Droge Hoodia sowie Zubereitungen, die aus Hoodia (Hoodia gor-
donii (MASSON) SWEET EX DECNE.) gewonnen werden, haben in den letzten zehn Jahren im-
side P57AS3 which was considered to mer mehr an Bedeutung gewonnen. Diese Nahrungsergänzungsmittel werden teilweise über das
be the active constituent of Hoodia gor- Internet verkauft und als Appetit zügelnde Präparate zur Gewichtsreduktion beworben. Das Wis-
donii [5]. Since then the publicity of sen um die sukkulente Pflanze stammt von Eingeborenen, dem Stamm der San. Diese leben seit
Jahrhunderten im Grossraum Südafrika und verwenden Hoodia als Bestandteil ihrer traditionel-
Hoodia began to develop with big ex-
len Medizin zur Unterdrückung von Durst und Hunger während ihrer Jagdausflüge. Zielsetzung:
pectations in the plant to be promoted Es soll eine Übersicht gegeben werden hinsichtlich des derzeit verfügbaren Wissens über Herkunft
successfully as anoretic drug. Several der Stammpflanze, chemische Zusammensetzung, Ethnopharmakologie und Pharmakologie von
herbal weight-loss products were for- Hoodia. Darüber hinaus werden die historische Entwicklung und rechtliche Fragen hinsichtlich des
geistigen Eigentums beleuchtet. Methoden: Systematische Auswertung der wissenschaftlichen
mulated hitherto and are sold as OTC
Literatur zu Hoodia aus den gängigen elektronischen Datenbanken. Ergebnisse: Bisher wurde
dietary supplements [5] but to date eine Reihe von Patenten zu Hoodia erteilt, von der behauptet wird, sie zügle den Appetit, be-
pharmaceutical industry has failed to sässe anti-diabetische Aktivität und zeige gastro-protektive Effekte infolge übermässiger Magen-

300 Schweiz. Zschr. GanzheitsMedizin 21 (6), Oktober 2009


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säuresekretion. Die ursprünglich geplante Entwicklung von Hoodia als Arzneimittel wurde 2004 was followed by a patent on pharma-
aufgegeben, in die Kategorie Nahrungsergänzungsmittel verschoben und mit Ende 2008 vorüber- ceutical compositions with appetite
gehend eingestellt. Die Kenntnis über die chemische Zusammensetzung konzentriert sich auf
Pregnanglykoside, von denen eine Verbindung als verantwortlich für die Wirkung angesehen wird. suppressant activity granted by the
Es wurden analytische Methoden entwickelt, die Screening-Untersuchungen der pflanzlichen World Intellectual Property Organisa-
Droge sowie von Formulierungen daraus erlauben. Bei einer grossen Anzahl von Nahrungsergän- tion in 1998 [10]. In 1998, the CSIR li-
zungsmitteln, die überprüft wurden und die vorgaben, Hoodia zu enthalten, konnten keine Pregnan- censed use of P57 to Phytopharm, a
glykoside detektiert werden. Diese Präparate gelten somit als Verfälschungen. Die Datenlage zu
den behaupteten gesundheitszuträglichen Wirkungen ist dünn. Es wurden die metabolische Sta- British pharmaceutical research com-
bilität des Hauptsteroidglykosids und dessen Wechselwirkung mit metabolisierenden Enzymen pany specialised in the development of
in vitro gemessen. In vivo zeigte diese Verbindung eine Reduktion der Kalorienaufnahme und des phytomedicines [4,9]. The aim was to
Körpergewichts nach intracerebroventrikularer Injektion oder oraler Gabe. Bis heute sind weder
promote the worldwide development
zu Klinik noch zur Toxikologie Daten in wissenschaftlich referierten Zeitschriften veröffentlicht.
Berichte über unerwünschte Wirkungen nach der Einnahme von Hoodia-haltigen Präparaten lie- and marketing of the patented extract
gen in zwei Fällen vor (anticholinerges Syndrom, akute Hepatitis). Schlussfolgerungen: Die P57 from Hoodia for suppressing ap-
gegenwärtige Datenlage zu Hoodia und Produkten daraus ist unzureichend. Das phytochemische petite, treatment of eating disorders,
Profil muss neben den bisher gut untersuchten Pregnanglykosiden noch eingehend auf weitere
adipositas and type-II-diabetes. The
Substanzklassen überprüft werden. Es gibt keine verlässlichen Angaben zu Toxizität, Sicherheit
und Klinik. Der Fall Hoodia ist untrennbar verbunden mit Fragen, die die Convention of Biological realisation of this ambitious project re-
Diversity (CBD) und den Artenschutz betreffen: Die mit den San unterzeichneten Übereinkommen quired the involvement of a solvent
zur Aufteilung eines potentiellen Gewinns sind international zu respektieren, ebenso wie die Tat- partner, therefore, Phytopharm sub-li-
sache, dass für Aufsammlung, Kultivierung, Transport oder Export behördliche Genehmigungen ein-
geholt werden müssen, da Hoodia unter Schutz steht.
censed the pharmaceutical giant Pfizer
in the very same year [4]. Press re-
Schlüsselwörter: Hoodia, San, Appetitzügler, Sicherheit, Qualitätskontrolle, Pharmakognosie
leases launched by Phytopharm re-
ported on completed pre-clinical stud-
ies (October 1998) and on a proof-of-
put a registered herbal remedy to the Botswana and, to a lesser extent, in principle clinical study with three suc-
market. The present paper reviews the South Africa. The San as well as other cessfully completed stages [11]. Al-
current scientific knowledge on Hoodia indigenous peoples in the region have though Phytopharm and Pfizer agreed
(Fig. 1) in terms of phytochemistry, sci- been using Hoodia and related species on a future development program for
entific evidence and health-related as a food and, especially, as a drink P57 in July 2002, only one year later
claims. A historic overview about the substitute and appetite suppressant, as Pfizer decided to discontinue its in-
succulent and its development as poten- well as for a variety of other purposes [4]. volvement upon the merger with Phar-
tial anoretic cure is given and intellec- The first reference to the use of macia, which resulted in the shutdown
tual property rights are addressed. Hoodia dates back to 1796 [6], whereas of its Natureceuticals group [4]. All
its use as thirst quencher and appetite rights were returned to Phytopharm
suppressant was recorded centuries who began discussions with potential
Historical development later [7, 8]. The above mentioned CSIR, licensing partners to develop the extract
South Africa’s national laboratory, had as a weight-control food supplement.
The commercialisation of biodiversity been established in 1945 by an act of In December 2004, Phytopharm en-
in Southern Africa was the topic of a Parliament in order to engage in in- tered together with Unilever into a li-
PhD study performed by WYNBERG at dustrial and scientific development to cence and joint development agree-
the University of Strathclyde, Scotland, improve the quality of life of African ment for the Hoodia extract [12], its de-
who laid down her compilation up to people [9]. This organisation obtained velopment as a pharmaceutical ceased.
the year 2004 in a detailed overview information about the properties of the The both companies aimed at bringing
[4]. According to WYNBERG, the San plant during a project on edible wild a new weight management product to
(Fig. 2) represent the oldest human in- plants and, therefore, included Hoodia the functional food market. The collab-
habitants in Southern Africa living in species in this project in 1963 [4]. Even oration comprised a five-stage pro-
small nomadic groups as hunters and though information from literature and gramme including safety and efficacy
gatherers for thousands of years. A laboratory tests on mice suggested studies. In September 2007, Phytopharm
long history of dispossession and relo- Hoodia as a promising non-toxic ap- announced the successful progress into
cation has accompanied the San which petite suppressant scientific evidence stage three, the final stage prior to sub-
started with their persecution upon to file for a patent was insufficient at mission for regulatory approval [13].
colonisation in 1652 followed by dis- that time. The issue was postponed un- However, data of a clinical study using
crimination along with other people of til further investigations including iso- Hoodia extract in a drink-based prod-
colour during South Africa’s apartheid lation and structure elucidation led to uct led Unilever to conclude that it is
regime and which continues today a “revival”: more than 30 years later, unsuitable to move forward with the
through permanent political marginal- in 1995, the CSIR was assigned a product concept [14]. In December 2008,
ization [4]. At present, the approxi- patent in South Africa which guaran- a mutual termination agreement was
mately 90.000 San in Southern Africa tees the use of the active components concluded between the parties and all
mainly live in the Kalahari Desert and of the plant – referred to as “P57” – re- the original Phytopharm patents and
its surrounding regions in Namibia, sponsible for suppressing appetite. This rights reverted to Phytopharm [14,15,

Schweiz. Zschr. GanzheitsMedizin 21 (6), Oktober 2009 301


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of biopiracy. Represented by the South Plant origin


African San Council, they filed suit
against the CSIR and its licensees [9] The genus Hoodia is classified as one
which, in March 2003, resulted in the of the stapeliads, a group of stem suc-
signing of an agreement between the culents belonging to the family Apocy-
two parties to share any royalties from naceae. They were formerly part of the
potential sales of drugs or other prod- family Asclepiadaceae, but are now as-
ucts derived from Hoodia [4,19]. The signed within the tribe Ceropegieae of
benefit sharing was arranged accord- the subfamily Asclepiadoideae to the
ing to the Convention on Biological Di- Apocynaceae [21]. The first Hoodia
versity (CBD) implemented 1992 at the species to be described were H. pilif-
Earth Summit in Rio de Janeiro [20]. era and H. gordonii, which were pub-
This “Global Convention” has 190 parties lished initially as Stapelia species in
and aims to achieve three objectives [20]: the second half of the 18th century. In
I The conservation of biological di- the 19th century, Stapelia pilifera L. f.
versity was moved to a new genus Tri-
I The sustainable use of its compo- chocaulon, and Stapelia gordonii was
nents published as Hoodia gordonii MASSON
I The fair and equitable sharing of be- [21]. According to a recent revision by
nefits from the use of genetic re- BRUYNS [22], the Trichocaulon species
sources. were regrouped into the genus Hoodia.
From the older literature it is clear
Under the terms of the agreement, the that Hoodia pilifera (=Trichocaulon pil-
CSIR will pay the San 8% of all pay- iferum = Stapelia pilifera) was the
ments it receives from its licensee, as species of choice for use as a substitute
well as 6% of all royalties once the drug for food and water given the vernacu-
is commercialised [18]. The money lar name “ghaap” [21]. The larger,
would be paid into a San-controlled hard-spined and more bitter tasting
Trust, tasked and committed to equi- species Hoodia gordonii is reported to
Fig. 1. Hoodia gordonii – natural habitat and table distribution of this money amongst be considered worthless in some re-
cultivation site in Biedouw-Valley, South Africa.
the San peoples [20]. gions, whereas in the Kalahari the
The Hoodia case attracted interna- pealed, juicy young shoots were eaten
16]. Even though Phytopharm’s func- tional attention because of its potential – raw and cooked – although it could
tional food programme was negatively to reduce appetite, because of being not be utilised in times of draught [21].
impacted by the Unilever decision not derived from an African plant, and, be-
to proceed, the company believes that cause it was one of the first times that
the pre-clinical and clinical data of the holders of traditional knowledge were
Hoodia extract encourage to continue given a share of the potential profits of
with further studies on obesity, as well products derived from that knowledge.
as for pharmaceutical and veterinary However, besides issues regarding patent
applications [14]. Presently Phytopharm law discussed in literature [9,2], the
is in early stage discussions with a benefit sharing agreement between the
number of interested partners. Expen- CSIR and the San implies further sub-
diture on the Hoodia programme will stantial political, environmental and
be limited until a satisfactory business ethical questions in intellectual prop-
proposition emerges [16,17]. erty law. MARTIN and VERMEYLEN analyse
whether or not intellectual property
rights can be used to advance the de-
Intellectual property rights velopment of indigenous peoples while
at the same time conserving their cul-
When the patent was awarded to the ture and their knowledge of nature
CSIR in 1998, this happened without [18]. SCHROEDER and CHENNELLS deal
the knowledge of the San [18]. They with the question whether benefit shar-
first learned of the patent through a ing could help the San who are exposed
Phytopharm press release [9]. Feeling to serious poverty, resulting in malnu-
exploited and disappointed, the San trition and avoidable illnesses, to over-
Fig. 2. San in a farm of the Ombili foundation
started opposition to the Hoodia patent come the lack of access to essential and trap for hunting as used by the San, Omu-
and accused the CSIR and Phytopharm health care [20]. ramba Ovambo valley, Namibia.

302 Schweiz. Zschr. GanzheitsMedizin 21 (6), Oktober 2009


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However, the existing literature mainly


O H3 C
deals with H. gordonii, and, to a lesser R2 O
CH3 CH3
extent with H. pilifera. In common with OR2
CH3 H
other Hoodia species, H. gordonii is a CH3 CH3
multi-stemmed succulent with thick,
erect, cylindrical, fleshy and fairly OH OH
hard, glabrous, grey-green to grey-
R1O R1O
brown stems [23]. The tubercles are
prominent, fused in their lower halves Isoramanone (R1=H, R2=H) Calogenin (R1=H, R2=H) 2
into 11–17 obtuse angles along stem, Hoodigogenin A (R1=H, R2=tigloyl) 1
P57AS3 (R=the-cym-cym-) 5
each tipped with a sharp spine 6–12mm
long [23]. H. gordonii has flesh-colour-
ed blooms as large as 75mm with an CH3 CH3
CH3 CH3
odour that resembles to rotten meat CH3 CH3
H OR2 H OR2
[24]. Due to its spines it is by mistake H H
H H
often referred to as “cactus”. The cul-
OH OH
tivation of the slow growing plant is not R1O OH R1O
CHO CHO
easy and must be started from seeds
[21,24]. Moreover, several Hoodia species Hoodistanal (R1=H, R2=H) 3 Dehydrohoodistanal (R1=H, R2=H) 4
are known to have small and widely
Fig. 3. Skeletal structures of Hoodia constituents.
dispersed populations [25], some of
them are listed as rare or vulnerable
in Red data lists [26]. Phytochemistry and duced to a hydroxyl function instead of
The planned commercialisation and quality control the ketone. A number of bisdesmosides
the wild harvesting of H. gordonii are (substitution in positions 3 and 20) and
considered as serious threat to rare The phytochemical papers published one monodesmoside (substitution in
Hoodia species which might be mis- hitherto focus on the two species H. position 3) have been isolated and
taken for H. gordonii. The danger of gordonii and H. pilifera [3,21,29–36]. called as hoodigosides L–V [32], Y and
overexploitation led to the inclusion of About forty different pregnane glyco- Z [36]. Most characteristic for the genus
Hoodia species to Appendix II of the sides have been isolated and struc- Hoodia are the rare 6-5-6-5 fused ring
Convention on International Trade in turally elucidated so far comprising the sterols hoodistanaloside A and B which
Endangered Species of Wild Fauna and aglycones hoodigogenin A (1), calo- are the first two naturally occurring
Flora (CITES) in 2005 [24, 27]. Anyone genin (2), hoodistanal (3) and dehydro- glycosides comprising a 5(6→7)abeo-
wishing to cultivate or harvest wild hoodistanal (4) (Meaning of the num- sterol aglycone (3, 4) [36]. A summary
Hoodia species outside of South Africa bers in brackets – see Fig. 3). of the isolated compounds is given in
must register for a CITES permit [24]. Hoodigogenin A (1) is a 3β,12β,14β- Table 1.
In South Africa, Hoodia species are pro- trihydroxy-pregn-5-en-20-one with a The limited availability of the plant
tected and permits are required from tigloyl ester substitution in position 12 material due to the above-mentioned
the authorities for the collection, culti- which is unique from Hoodia [36]. The reasons and the increasing popularity
vation, transport or exporting of the derivatives of hoodigogenin A repre- leads to the problem of adulterations.
plants [21]. In 2005, the Cape Ethno sent 3β-O-glycosides with a chain con- In the US for example, more than 100
Botanical Growers Association was sisting of two to five sugar moieties products are currently marketed as
founded due to threat of Hoodia be- named hoodigosides A–K [21,32], W tablets, capsules, liquid gels, liquid
coming extinct [28] with the aim to and X [36] and gordonosides A–L [30]. tinctures, snack bars, juice, powders,
guarantee the supply with plant mate- The distinction between these closely protein shakes, lollipops, tea and cof-
rial and to prevent unregulated collec- related compounds is made by the sug- fee [37]. Such Hoodia products – partly
tion upon the increasing interest in the ars, mainly D-glucose as well as 6-de- offered on the Internet – are outside
commercial application of Hoodia. In oxy- and 2,6-dideoxy sugars such as D- the profit sharing agreement, which is
2006, this organisation merged with thevetose, D-cymarose, D-oleandrose, appealed against by lawyers repre-
the Southern African Hoodia Growers D-digitoxose and 3-O-methyl-6-deoxy- senting the San [19]. As the supply of
Association in order to include Hoodia D-allose [21,33]. One of the first hood- authentic H. gordonii cannot match the
cultivators from Namibia and Botswana igosides to be published and patented demand for all these preparations,
[28]. This newly formed Southern African was named P57AS3 (5), it is regarded adulterations by other species or even
Hoodia Association signed a profit shar- as the active principle in Hoodia and genera occur [37]. Consequently, ana-
ing agreement with the San in Febru- sometimes referred to as P57. In com- lytical techniques have been developed
ary 2006 [19,28]. parison to hoodigogenin A (1), calo- based on the acquired knowledge on
genin (2) lacks the hydroxygroup in po- the plant’s composition in order to de-
sition 12β and exhibits position 20 re- tect appearing adulterations. HPLC-UV

Schweiz. Zschr. GanzheitsMedizin 21 (6), Oktober 2009 303


Übersichtsarbeit R Review Article

Tab. 1. Constituents identified in Hoodia

Synonym accor- Ref. No MW Aglycone R1 R2


ding to Reference in Ref.
Gordonoside A 30 1 430 Hoodigogenine A H tigloyl-
Hoodigogenine A 31 1a
Hoodigoside A 31 1 734 Hoodigogenine A the-cym- tigloyl-
P57AS3 31 12 878 Hoodigogenine A the-cym-cym- tigloyl-
Compound 1 3 1
Formula 6 33 6
Hoodigoside B 31 2 894 Hoodigogenine A the-the-cym- tigloyl-
Hoodigoside C 31 3 1022 Hoodigogenine A the-cym-cym-cym- tigloyl-
Gordonoside C 30 3
Hoodigoside D 31 4 1038 Hoodigogenine A the-the-cym-cym- tigloyl-
Compound 2 3 2 1022 Hoodigogenine A cym-the-cym-cym- tigloyl-
Hoodigoside E 31 5 1040 Hoodigogenine A glc-the-cym-cym- tigloyl-
Gordonoside H 30 8
Hoodigoside F 31 6 1084 Hoodigogenine A glc-ole-the-cym-cym- tigloyl-
Hoodigoside G 31 7 1084 Hoodigogenine A glc-cym-the-cym-cym- tigloyl-
Hoodigoside H 31 8 1068 Hoodigogenine A glc-cym-cym-cym-cym- tigloyl-
Hoodigoside I 31 9 1068 Hoodigogenine A glc-ole-cym-cym-cym- tigloyl-
Hoodigoside J 31 10 1154 Hoodigogenine A glc-ole-dig-cym-cym- tigloyl-
Hoodigoside K 31 11 898 Hoodigogenine A glc-glc-cym- tigloyl-
Hoodigoside L 32 1 1206 Calogenin (4-O-tigloyl)-the-ole glc-glc-glc-
Hoodigoside M 32 3 1124 Calogenin the-ole- glc-glc-glc-
Hoodigoside N 32 4 638 Calogenin the-ole- H
Hoodigoside O 32 5 1044 Calogenin (4-O-tigloyl)-the-ole glc-glc-
Hoodigoside P 32 6 1190 Calogenin (4-O-tigloyl)-ole-cym glc-glc-glc-
Hoodigoside Q 32 7 1350 Calogenin (4-O-tigloyl)-the-cym-cym- glc-glc-glc-
Hoodigoside R 32 8 1334 Calogenin (4-O-tigloyl)-ole-cym-cym- glc-glc-glc-
Hoodigoside S 32 9 1478 Calogenin (4-O-tigloyl)-ole-cym-cym-cym- glc-glc-glc-
Hoodigoside T 32 10 1316 Calogenin (4-O-tigloyl)-ole-cym-cym-cym- glc-glc-
Hoodigoside U 32 11 1478 Calogenin (4-O-tigloyl)-cym-cym-cym-cym- glc-glc-glc-
Hoodigoside V 36 6 882 Calogenin (4-O-tigloyl)-the-ole- glc
Compound 2 32 2
Hoodigoside W 36 1 1022 Hoodigogenine A ole-the-cym-cym- tigloyl-
Hoodigoside X 36 2 796 Isoramanone the-cym-cym- H
Hoodigoside Y 36 5 800 Calogenin the-ole- glc
Hoodigoside Z 36 7 1026 Calogenin (4-O-tigloyl)-the-the-ole- glc
Hoodistanaloside A 36 8 914 Dehydrohoodistanal (4-O-tigloyl)-the-ole- glc
Hoodistanaloside B 36 9 896 Hoodistanal (4-O-tigloyl)-the-ole- glc
Gordonoside B 30 2 1022 Hoodigogenine A the-ole-cym-cym- tigloyl-
Gordonoside D 30 4 992 Hoodigogenine A dig-ole-cym-cym- tigloyl-
Gordonoside E 30 5 1006 Hoodigogenine A ole-ole-cym-cym- tigloyl-
Gordonoside F 30 6 1006 Hoodigogenine A ole-cym-cym-cym- tigloyl-
Formula 9 33 9
Gordonoside G 30 7 1006 Hoodigogenine A cym-cym-cym-cym- tigloyl-
Formula 10 33 10
Gordonoside I 30 9 1136 Hoodigogenine A dig-ole-ole-cym-cym- tigloyl-
Gordonoside L 30 10 1150 Hoodigogenine A ole-cym-cym-cym-cym- tigloyl-
Formula 11 33 11
Formula 7 33 7 1018 Hoodigogenine A cym-mda-cym-cym- tigloyl-
Formula 8 33 8 992 Hoodigogenine A ole-dig-cym-cym- tigloyl-
Formula 12 33 12 1022 Hoodigogenine A ole-mda-cym-cym- tigloyl-
cym: β-D-cymarose; dig: β-D-digitoxose; glc: β-D-glucose; mda: 3-O-methyl-6-deoxyallose; ole: β-D-oleandrose; the: β-D-thevetose;
Ref: reference; MW: molecular weight

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[38], HPLC-MS [39], UPLC-UV-MS [37] port and absorption [41]. The authors Conclusions
and HPTLC [5] are useful methods to conclude that the intestinal transport
perform qualitative analysis and to of P57AS3 is mediated by P-glycopro- Hoodia has been of increasing interest
quantify respective steroid glycosides tein and multidrug resistance-associ- within the past decade due to its at-
[40] from H. gordonii preparations. ated protein transporters. The com- tractive indication profile. It originates
The new methods developed for chem- pound was metabolically stable and from Southern African indigenes, the
ical fingerprint analysis allow a quick showed weak inhibition of CYP 3A4 [41]. San, who have been using the plant
and reliable assessment of various ma- A study in rats showed that the intra- since centuries as thirst and appetite
trices: Hoodia species, plants from gen- cerebroventricular injection of P57AS3 quencher. The South African Council
era related to Hoodia and dietary sup- (0.07 mg 5 per injection) reduced the for Scientific and Industrial Research
plements that claim to contain H. gor- food-intake during 24h after extract (CSIR) together with the British com-
donii may be screened. According to application by 40–60%. The effect was pany Phytopharm have been aiming at
RUMALLA et al., the HPTLC analysis of dose-dependent and suggested a likely the development of Hoodia as phar-
thirteen commercially available dietary central (CNS) mechanism of action for maceutical or food supplement but
supplements confirmed the presence of P57AS3 [42]. In a later study this com- were not successful to date. Meanwhile
H. gordonii for only two samples, pound was applied orally to rats over a considerable amount of patents has
eleven products did not show any of the a three-day period (6.25–50 mg/kg). been issued protecting the rights on an
scrutinised pregnane glycosides [5]. Compared to the animals who were extract and compounds out of Hoodia
Quantification analyses showed vari- either treated with the vehicle or with for its appetite reducing, anti-diabetic
ability and big differences in the con- the appetite suppressor fenfluramine and gastro-protective activity. Benefit
tents: an extract of dried H. gordonii was food consumption and body mass gain sharing agreements with the San have
determined by 2.1% of total steroid gly- of the P57AS3 treated rats decreased been signed in order to share in profit
cosides [40]. The content of the single significantly during a monitoring period from cultivation and potential commer-
compound P57AS3 (5) was found to be of eight days [3]. cialisation of Hoodia. To prevent the
0.05% and 0.005% in two H. gordonii The utmost recent patent filed by slow-growing plant from over exploit-
plant samples. Two of ten commercially Unilever reports on polysaccharides ation and to guarantee sustainable
available dietary supplements which obtainable from plants of the Asclepi- supply, Hoodia species were included
claimed to consist of H. gordonii con- adoideae subfamily (Hoodia, H. gordo- into Appendix II of the Convention on
tained 0.17% and 0.005% of P57AS3, nii, Stapelia) which are said to exhibit International Trade in Endangered
but in the remaining eight prepara- a not otherwise specified immunostim- Species of Wild Fauna and Flora (CITES).
tions it was not detectable at all [39]. ulating effect [43]. Collection, cultivation, transport and
These data show the diverse quality of According to the author’s knowl- export are subjected to strict rules
the offered products and should raise edge, no papers in peer-reviewed jour- which need to be respected by all coun-
the consumer’s awareness of potential nals have been published to date on tries who signed the Convention of Bio-
adulterations because they represent a clinical trials with Hoodia. The only logical Diversity (CBD). However, obe-
potential health risk. available information are press re- sity concerns many people in the civi-
leases by Phytopharm which report on lized countries and as presently only
a double-blind, placebo-controlled clini- few drugs are available to treat this
Effects, mode of action, cal study on overweight male volun- condition efficiently a break-through
clinical trials teers who showed a statistically signif- would open a big potential market.
icant reduction in the average daily Some institutions see this chance and
The main reason why Hoodia became calorie intake and in body fat [11,13]. provide Hoodia preparations disregard-
so popular within the last decade is its There is scarce evidence in literature ing the above-mentioned patents and
use for suppressing appetite. Various about serious adverse effects. A recent agreements even though there are no
patents were filed comprising extracts, publication from Italy reports on prepa- data on successful clinical studies.
constituents and preparations of H. rations containing Hoodia and con- Preparations are available in Europe
gordonii which cover suppression of comitant drugs related to one case of and the US. Valuable phytochemical in-
appetite, anti-diabetic activity and treat- acute hepatitis and one case of anti- vestigations focusing on one class of
ment of gastric acid secretion damage. cholinergic syndrome [44]. compounds, the pregnane glycosides,
However, there is little data on Hoodia’s Recently a monograph of H. gordonii allow the quality control of the crude
mechanism of action even though this has been prepared and compiled by drug and preparations containing
would be of substantial interest. The VAN WYK. The monograph on general Hoodia. The results of these screenings
metabolic stability of P57AS3 (5) in hu- description, identity/quality, use/efficacy give rise to serious concern about the
man liver microsomes and its interac- and safety is planned to be published safety of such products as a consider-
tion with drug metabolising enzymes in the African Herbal Pharmacopoeia able amount seems to lack Hoodia.
were determined [41]. Intestinal trans- by the third quarter of 2009 [45]. Even though Hoodia itself might be
port of P57AS3 was studied in the safe, if slim-down products claimed to
Caco-2 cell model of intestinal trans- contain Hoodia obviously lack this

Schweiz. Zschr. GanzheitsMedizin 21 (6), Oktober 2009 305


Übersichtsarbeit R Review Article

agent, what else do these preparations 10 Van Heerden FR, Vleggaar R, Horak RM, Lear- 33 Abrahamse SL, Povey KF, Rees DD. Appetite
month RA, Maharaj V, Whittal RD: Steroidal gly- suppressant compositions. 2007: patent; WO
contain? This involves a clear safety cosides, methods for their production and prepa- 2007096239.
risk and has to be assessed critically. ration, pharmaceutical compositions containing 34 Shukla YJ, Fronczek FR, Pawar RS, Khan IA.
them, and their use as appetite suppressants. Hoodigogenin A from Hoodia gordonii. 2008:
The consumers’ attention should be 1998: patent; WO9846243. Acta Cryst E64; o1643–o1644.
drawn to the fact that they run danger 11 Phytopharm pld, Successful Completion of Proof 35 Avula B, Wnag YH, Pawar RS, Shukla YJ, Smillie
of Principle Clinical Study of P57 for Obesity, TJ, Khan IA. Identification and structural charac-
to be affected by adverse reactions due Press release, 5 Dec 2001; available at: www. terization of steroidal glycosides in Hoodia gor-
to unspecified constituents with a com- Phytopharm.co.uk/press (accessed Sept 14th donii by ion-trap tandem mass spectrometry and
2005). liquid chromatography coupled with electrospray
pletely unknown chemical and phar- 12 Phytopharm and Unilever enter into a Licence ionization time-of-flight mass spectrometry.
macological profile. Who would take and Joint Development Agreement for Hoodia Rapid Com Mass Spec 2008;22:2587–2596.
gordonii Extract, Press release, 15 Dec 2004; 36 Shukla YJ, Pawar RS, Ding Y, Li XC, Ferreira D,
the responsibility in this case? available at: www.phytopharm.co.uk/news/ Khan IA. Pregnane glycosides from Hoodia gor-
Apart from this ethical issue, several newsreleases (accessed May 18th 2009). donii. Phytochemistry 2009;70:675–683.
13 Phytopharm, Portfolio, Weightmanagement Hoodia 37 Avula B, Wang YH, Pawar RS, Shukla YJ, Smillie
other questions remain open: Why did extract; available at: www.phytopharm. com/port- TJ, Khan IA: A rapid method for chemical finger-
two big companies who participated in folio/?id=2244 (accessed May 18th 2009). print analysis of Hoodia species, related genera,
14 Neutraceuticals World, Braking News, Unilever and dietary supplements using UPLC-UV-MS. J
the development abandon? Why did abandons hoodia project; available at: http:// Pharm Biomed Anal 2008;48:722–731.
they not succeed in publishing data www.nutraceuticalsworld.com/news/2008/11/2 38 Avula B, Wang YH, Pawar RS, Shukla YJ, Khan
6 (accessed June 24th 2009). IA: Chemical Fingerprinting of Hoodia Species
about safety, toxicology and clinics? 15 Phyotpharm, News, News Releases, Unilever and Related Genera: Chemical Analysis of
Does Hoodia have an effect or not? returns rights to Hoodia extract, Press release, 12 Oxypregnane Glycosides Using High-
Dec 2008; available at: www.phytopharm. Performance Liquid Chromatography with UV
Which other compounds are contained com/news/newsreleases/?id=16553 (accessed Detection in Hoodia gordonii. Journal of AOAC
in Hoodia and what effects/adverse ef- June 24th 2009). International 2007;90(6): 1526–1531.
16 Phyotpharm, News, News Releases, Interim 39 Avula B, Wang YH, Pawar RS, Shukla YJ,
fects do they have? To date, we are not Management Statement for the three month Schaneberg B, Khan IA: Determination of the
able to answer these questions but sup- period ended 31 December 2008, Press release, Appetite Suppressant P57 in Hoodia gordonii
17 Feb 2009; available at: www.phytopharm. Plant Extracts and Dietary Supplements by
pliers, customers as well as govern- com/news/newsreleases/ ?id=16706 (accessed Liquid Chromatography/Electrospray Ionization
ments should not forget about the sen- June 24th 2009). Mass Spectrometry (LC-MSD-TOF) and LC-UV
17 Phyotpharm, News, News Releases, Interim Methods. Journal of AOAC International
sitive background of this potential Results for the six months ended 31 March 2006;89(3):606–611.
“slimming agent”. 2009, Press release, 20 May 2009; available at: 40 Janssen HG, Swindells C, Gunning P, Wang W,
www.phytopharm.com/news/newsreleases/ Grün C, Mahabir K, Maharaj VJ, Apps PJ:
?id=17403 (accessed June 24th 2009). Quantification of appetite suppressing steroid
Acknowledgements 18 Martin G, Vermeylen S: Intellectual Property, glycosides from Hoodia gordonii in dried plant
My thanks go to Prof. K. Eloff, Prof. B-E. Van Indigenous Knowledge, and Biodiversity. Capital- material, purified extracts and food products
ism Nature Socialism 2005;(16)3:27–48. using HPLC-UF and HPLC-MS methods. Anal
Wyk and Dr. T. Brendler for their willingness
19 Anonymous: Protecting traditional knowledge: Chim Act 2008;617;200–207.
and promptness to answer my questions
the San and hoodia. Bulletin of the World Health 41 Madgula VLM, Avula B., Pawar RS, Shukla YJ,
concerning the Hoodia monograph in the Organization 2006;84(5):345. Khan IA, Walker LA, Khan SI: In Vitro Metabolic
African Herbal Pharmacopoeia. Dr. F. Peter- 20 Schoeder D, Chennells R: Benefit sharing and Stability and Intestinal Transport of P57AS3 (P57)
sen took his time to discuss the Hoodia is- access to essential health care: a happy mar- from Hoodia gordonii and its Interaction with
sue with me, which helped a lot. I am deeply riage? Medicine and Law 2008;27(1):53–69. Drug Metabolizing Enzymes. Planta Med
indebted to DI. W. Wurzinger and Dr. Ch. 21 Van Heerden FR. Hoodia gordonii: A natural 2008;74:1269–1275.
Reisch for providing me with photographs. appetite suppressant. J Ethnopharmacol 2008; 42 MacLean DB, Luo LG: Increased ATP content/ pro-
119:434–437. duction in the hypothalamus may be a signal for
22 Bruyns PV: A revision of Hoodia and Lavrania energy-sensing of satiety: studies of the anorec-
(Asclepiadaceae-Stapelieae). Botanische Jahr- tic mechanism of a plant steroidal glycoside.
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306 Schweiz. Zschr. GanzheitsMedizin 21 (6), Oktober 2009

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