Hoodia
Hoodia gordonii (Masson) Sweet ex Decne. Family: Apocynaceae (dogbane)
Bushman's hat , queen of the Namib , xhoba (San)
 
Clinical Overview
Uses
Hoodia products have been marketed worldwide for weight loss; however, there appears to be little quality control or protection of the endangered source plant.

Dosing
There is no published research to support dosages of the herb.

Contraindications
No information is available.

Pregnancy/Lactation
There are no known concerns with pregnancy and lactation.

Interactions
None well documented.

Adverse Reactions
No adverse reactions have been reported.

Toxicology
No toxicology data is available.

 
Botany
H. gordonii is a rare, succulent plant found in the Kalahari Desert of southern Africa. The leafless, swollen, spiny stem is similar to that of a columnar cactus, and is topped by showy, saucer-shaped flowers. The flowers emit a carrion-like odor that attracts pollinating insects. It is considered an endangered species because of the high potential for over-exploitation and is listed in Appendix II of Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Commercial plantations have been established in South Africa to provide for anticipated demand for the plant, although the slow growth of the plant may make commercial cultivation difficult. 1 Hoodia was formerly in the Asclepiadaceae (milkweed) family, but it has recently been subsumed into the Apocynaceae (dogbane) family. 2 Other species in the genera Hoodia and Trichocaulon have been claimed to have similar biological activity to H. gordonii . 3
 
History
Hoodia was not well known to the Western world until recently. Ethnobotanical reports date back to 1796; however, Hoodia received little attention until a South African scientific project evaluated its appetite suppressant effects in 1963. 4,  Modern techniques of structure analysis revealed the bioactive molecule P57 in the 1980s. As a result, a patent was filed by the Council for Scientific and Industrial Research (CSIR) in 1995 in South Africa. 3 At the same time, a licensing agreement was signed between CSIR and the company. A sublicense was granted to Pfizer for further clinical development of P57, which Pfizer relinquished in 2003. In 2003, CSIR responded to criticism of its appropriation of San (southern Africa's oldest human inhabitants) indigenous knowledge by signing a memorandum of understanding with the South African San Council. That provided for benefit sharing of Hoodia royalties. 4 In the meantime, a thriving, apparently illicit, worldwide market has emerged that offers Hoodia herbal products as dietary supplements.
 
Chemistry
The active appetite suppressant principle of H. gordonii is P57, a pregnane steroid glycoside with 3 saccharides and a tiglate ester. 3 The details of structure elucidation have not been published outside of the patent literature; however, a recent meeting presentation reported isolation of 13 oxypregnanes from H. gordonii . 5 Other presentations at this meeting disclosed methods for thin layer chromatographic analysis of Hoodia , 6,  polymerase chain reaction identification methods, 7,  and microscopic identification. 8,  A high-performance liquid chromatography mass spectrometry method for analysis of P57 has also been reported. 9
 
Uses and Pharmacology
There is a single published report concerning the pharmacology of Hoodia and P57. Intracerebroventricular injection of P57 into male rats reduced food intake 50% to 60% over a 24-hour period. Similar experiments with the aglycone or a second analog had no effect, nor did intraperitoneal injections of P57. P57 was inactive against Na/K adenosine triphosphatase (ATPase), despite having a structure with some similarity to the cardiac glycosides found in the same plant family. 10,  Investigators detected an increase in hypothalamic adenosine triphosphate (ATP) content for rats on a normal diet when P57 was administered intracerebroventricularly. Hypothalamic ATP levels dropped in untreated rats fed a hypocaloric diet; P57 reversed this reduction. 10 Thus, it appears that P57 may operate through normalization of hypothalamic ATP levels to produce anorexia.
The patent makes reference to an agonistic effect of P57 on the melanocortin-4 receptor 3,  ; melanocortin-4 (MCR-4) agonists have been considered as potential treatment for obesity by the pharmaceutical industry. 11,  However, the complex pharmacology of the melanocortin receptor family has made manipulation of this system difficult. The patent claims that MCR-4 receptor agonism regulates neuropeptide Y and increases cholcystikinin have not been reported in peer-reviewed journals. 3
In addition, patents claim Hoodia products are useful in control of gastric acid secretion 12,  and treatment of diabetes. 13
 
Administration & Dosage
Poorly documented clinical trials are reported to have proof of concept for weight loss, 4 but scientific basis is lacking. There is no published research to support dosages of the herb.
 
Pregnancy/Lactation
There are no known concerns with pregnancy and lactation.
 
Interactions
None well documented.
 
Adverse Reactions
No adverse reactions have been reported.
 
Toxicology
There is no documentation for the safety of Hoodia , although its demonstrated inactivity against Na/K ATPase mitigates concerns about the potential for cardiotoxicity. 10
 
References
 

1. Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES). Appendices I, II, and III. Available at: http://www.cites.org/eng/app/appendices.pdf . Accessed January 10, 2006.

 

2. Sennblad B , Bremer B . Classification of Apocynaceae s.l. according to a new approach combining Linnaean and phylogenetic taxonomy. Syst Biol . 2002;51:389-409.  PubMed

 

3. van Heerden FR , Vleggaar R , Horak RM , et al. Pharmaceutical compositions having appetite suppressant activity. 2002;US Patent No. 6376657.

 

4. Wynberg R . Rhetoric, realism and benefit-sharing: use of traditional knowledge of Hoodia species in the development of an appetite supressant. J World Intellect Prop . 2004;7:851-876.

 

5. Pawar RS , Shukla Y , Avula B , Wang Y-H , Khan IA . Isolation of oxypregnane glycosides from Hoodia gordonii . Poster presented at: Annual Meeting of the American Society of Pharmacognosy; August 5-9, 2006; Arlington, VA.

 

6. Ikenouye LM , Gourdin GT , McChesney JD , Verbitski SM . Thin layer chromatography and Bioluminex identification of Hoodia gordonii . Poster presented at: Annual Meeting of the American Society of Pharmacognosy; August 5-9, 2006; Arlington, VA.

 

7. Techen N , Khan IA , Scheffler BE . The use of polymerase chain reaction (PCR) for the identification of Hoodia spp. Poster presented at: Annual Meeting of the American Society of Pharmacognosy; August 5-9, 2006; Arlington, VA.

 

8. Joshi VC , Khan IA . Authentication of weight loss botanical Hoodia gordonii sweet and its possible substitutes. Poster presented at: Annual Meeting of the American Society of Pharmacognosy; August 5-9, 2006; Arlington, VA.

 

9. Avula B , Wang YH , Pawar RS , Shukla YJ , Schanebert B , Khan IA . 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 . 2006;89:606-611.  PubMed

 

10. MacLean DB , Luo LG . 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 Res . 2004;1020:1-11.

 

11. Nargund RP , Strack AM , Fong TM . Melanocortin-4 receptor (MC4R) agonists for the treatment of obesity. J Med Chem . 2006;49:4035-4043.  PubMed

 

12. Hakkinen J , et al. Gastric acid secretion. US patent 6 488 967. 2002.

 

13. Rubin ID , et al. Extracts, compounds & pharmaceutical compositions having anti-diabetic activity and their use. US patent 7 033 616. 2006.