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Hoodia Gordonii (HOODIA), a TRADITIONAL APPETITE SUPPRESSANT

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Hoodia Gordonii (HOODIA), a TRADITIONAL APPETITE SUPPRESSANT Cox A G et al. / Pharmacie Globale (IJCP) 2011, 7 (10) Available online at www.pharmacie-globale.info ISSN 0976-8157 Review Article PHARMACIE GLOBALE INTERNATIONAL JOURNAL OF COMPREHENSIVE PHARMACY PHARMACOGNOSY OF THE HERBAL MEDICINE Hoodia gordonii (HOODIA), A TRADITIONAL APPETITE SUPPRESSANT Arthur G Cox* and Samit Shah Department of Pharmaceutical Sciences, South University School of Pharmacy, Savannah GA, USA. Received: 8 May 2011; Revised: 25 June 2011; Accepted: 30 June 2011; Available online: 5 July 2011 ABSTRACT Obesity is now at epidemic proportions throughout the world. It is known to be associated with a number of diseases and is one of the leading preventable causes of death worldwide. Development of herbal and synthetic agents for the treatment of obesity represents a potential multi-billion dollar market. Previously marketed herbal and synthetic weight loss medications have suffered from serious potential adverse reactions. Hoodia gordonii is a cactus-like plant traditionally used by natives of Africa to suppress hunger pangs during long hunting trips. Constituents of hoodia may represent anti-obesity lead compounds that work by mechanisms not previously exploited. Two multi-national pharmaceutical companies have invested several tens of millions of dollars in development of these agents. By fractionation of extracts of hoodia, and biological assay of the fractions, the14- hydroxy pregnane glycoside P57 has been isolated. A number of studies have provided support for development of the crude plant extract and isolation of P57 into clinically useful appetite suppressants for the treatment of obesity. Some controversy surrounds the development of hoodia into commercial medicinal or dietary substances, due to potential infringement on “traditional intellectual property”. Furthermore, questions remain regarding the efficacy of these preparations, their mechanism of biological action, and their safety. The present review summarizes the current knowledge surrounding these questions, within a historical context of drug development. Keywords: Hoodia gordonii, Appetite Suppressant, Pharmacognosy, P57, Plant Steroidal Glycoside. INTRODUCTION Excessive body weight is known to be associated with a nervousness, insomnia, hypertension, and irregular number of diseases, such as diabetes and heart disease, heartbeat. For the preceding reasons, a weight loss and is one of the leading preventable causes of death product that does not work by sympathomimetic action is worldwide.1 Reduction in caloric intake is one of the desirable. The herbal medicine commonly called “hoodia” mainstays of reducing excessive body weight. However, may be a viable alternative, and many hoodia-containing many individuals have difficulty adhering to a reduced preparations have been extensively marketed.5 More than calorie diet. For this reason, there is considerable demand 100 products have been marketed in formulations ranging for products that can decrease appetite. Previously from tablets and tinctures to protein shakes and lollipops.6 popular herbal and synthetic weight-loss products, such as Much of the early marketing notoriously occurred through ephedra, phenylpropanolamine, and sibutramine have spam email. been found to be associated with serious adverse effects. Hoodia is derived from plants in the genus Hoodia, Phenylpropanolamine has been removed from the market especially Hoodia gordonii. H. gordonii was discovered in a number of countries due to increased risk of and described by Col. Robert Gordon Jackson in 1779. It 2 hemorrhagic stroke. The more recently developed anti- was initially identified as a member of the closely related obesity drug sibutramine has also been withdrawn from genus Stapelia and named Stapelia gordonii in his honor. 3 the market due to adverse cardiovascular events. Later it was moved to the genus Hoodia, which itself was Ephedra (Ephedra sineca) plant material, which has been named in honor of Van Hood, a renowned succulent widely used in herbal weight loss products, has similarly grower of the 19th century. been associated with adverse cardiovascular and central nervous system events.4 This has led to a ban on its use in Hoodia species are found in the arid west of Southern the United States. Ephedra alkaloids, sibutramine, and Africa and Namibia. Common names for the plant include phenylpropanolamine are all sympathomimetic agents, Bushman's hat, queen of the Namib, and xhoba. Hoodia has and may produce side effects typical of stimulants, such as traditionally been used by the San people of South Africa and Namibia to suppress appetite and thirst during long *Corresponding Author: 7 Arthur G Cox hunting trips in the Kalahari desert. Hoodia species are in Assistant Professor, Department of Pharmaceutical Sciences, the Apocynaceae, or dogbane family, within the subfamily South University School of Pharmacy, 709 Mall Boulevard, Asclepiadoideae. The general growth pattern is as a small Savannah GA, 31406, The United States. shrub-like succulent (up to 1 m high) with large flowers Contact no: +91-22018133; Email: [email protected] 1 Pharmacie Globale© (IJCP), Vol. 02, Issue 07 Cox A G et al. / Pharmacie Globale (IJCP) 2011, 7 (10) (up to 75 mm) which often have a strong carrion smell. (WIMSA) for misappropriation of intellectual property This smell attracts flies and other pollinators. They are rights of the native San people (i.e. “biopiracy”). WIMSA very tolerant to harsh growing conditions, growing in was established in 1996 at the request of the San people in temperature extremes of -3°C to +40°C in dry sands and South Africa, Botswana, Namibia, Zambia, and Zimbabwe stony soils. Initial growth form occurs as a single stem, to provide a platform for their communities to express which branches as the plants mature. Asclepiadoideae their concerns and advocate for their rights.13 It has been contains close to 3000 species within 415 genera. Its reported that CSIR was originally informed of the appetite members range in form from lianas to trees. They are suppressant activity by members of the San, and thus mostly tropical or warm temperate, with distribution commercialization of hoodia warrented just compensation largely in Africa and South America. Modern plant for those peoples.14 systematics puts hoodia into the subfamily (often referred WIMSA was influential in effecting a “benefit sharing” 8 to as family) Asclepiadaceae. Hoodia belongs to the tribe agreement between the CSIR and the San representatives Stapeliae within Asclepiadeaceae. The various species of in 2003. This agreement is widely acknowledged to be one Stapeliae have the general appearance of a cactus, being of the most important examples of an indigenous people leafless and succulent. Spines on the stem of the plant obtaining financial benefits through a benefit sharing (spiny tubercles) provide further resemblance to cacti agreement.15 Benefit sharing is a term popularized by the (Figure 1). Although hoodia species resemble cacti Convention on Biological Diversity (CBD) adopted at the (Cactaceae), they are not closely related, but rather owe 1992 Earth Summit in Rio de Janeiro, Brazil.16 Signatories their similar morphology to convergent evolution. of the CBD require users of plant and animal resources to Figure 1. A young Hoodia gordonii growing in its share the benefits with those who provide knowledge of natural environment. Flies have been attracted to the and access to genetic resources. As a result of this plant by the carrion-like smell of the flowers, and may agreement, a San Hoodia Trust was founded and charged help pollinate it. with acting on behalf of WIMSA to ensure the proper distribution of financial benefits derived from Hoodia. In contrast to Phytopharm’s patent for appetite suppression from hoodia extract, use of the plant itself is not protected. For this reason there have been a profusion of commercial products claiming to contain hoodia, although this claim is often suspect. Lack of standardization of active constituents, lack of control of purity, and lack of control over manufacturing conditions are some of the obstacles to rational comparision of the commercial products. Pfizer returned development rights to Phytopharm in 2003 without commercializing hoodia, and stopped efforts to further develop it as a pharmaceutical. A spokesperson for Pfizer stated that development was halted due to difficulty of synthesizing hoodia. Given the potential multi- billion dollar market for an effective diet aid, it seems surprising that synthetic difficulty alone might be a primary reason to abandon hoodia. However, Jasjit S. Bindra, a lead researcher on hoodia at Pfizer, acknowledged that early clinical trials showed that hoodia *Image copyright Martin Heigan, 2006. Used with permission. could be a potent appetite suppressant, but there were MODERN DISCOVERY OF ACTIVITY indications of effects on the liver that could not be easily In the early 1960s The Center for Scientific and Industrial removed from the supplement. He concluded that “Clearly, Research (CSIR) of South Africa began investigations into hoodia has a long way to go before it can earn approval the nutritional properties and possible long term toxicity from the Food and Drug Administration. Until safer of plants traditionally used as indigenous subsistence formulations are developed, dieters should be wary of “bush foods”. In these studies it was found that extracts of using it”.17 In 2005, Phytopharm granted an exclusive Hoodia species, particularly H. gordonii
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