Hoodia

 Vermaak I, Hamman JH, Viljoen AM. Hoodia gordonii: an up-to-date review of a commercially important anti-obesity plant. Planta Med. July 2011;77(11):1149-1160.

Hoodia (Hoodia gordonii) is used traditionally in Africa as an appetite and thirst suppressant. Due to this activity, hoodia has been widely used as a supplement to treat obesity. Of particular interest is the pregnane glycoside P57, found to be active against obesity. Despite evidence of efficacy, controversy surrounding hoodia is widespread due to adulteration of supplements; problems associated with availability include slow growth cycle and subsequent scarcity of the plant, tightly regulated harvesting, and consumer popularity. This review aimed to profile the state of hoodia phytochemicals and general scientific research.

Hoodia, part of the Apocynaceae family, is a succulent characterized by thorns, grey-brown stems, and big flowers. Hoodia grows in western South Africa and Namibia, and although it is tolerant of many conditions, it is slow to grow and cultivate. Small pieces of the fresh peeled stems of several Hoodia species (including H. gordonii, H. currorii, H. flava, and H. pilifera) are traditionally used by the Khoi-San people to suppress hunger and thirst during long hunts or times of little food, as well as for the treatment of hypertension, diabetes, and other conditions.

The Council for Scientific and Industrial Research (CSIR) conducted several studies on hoodia and isolated the bioactive compound P57. A patent to CSIR was given for this compound with appetite suppression activity by the World Intellectual Property Organization, and licensing for P57 development was passed down through various pharmaceutical companies. Supposed roadblocks to the further development of P57 were problems with synthesis, safety, and efficacy. After a complex legal battle, the Khoi-San now hold intellectual property rights for hoodia and have a financial stake in any development of the plant.

In addition to P57, other similar compounds have been isolated from hoodia. The shared backbone structures of these compounds are the aglycones hoodigogenin A, calogenin, hoodistanal, dehydrohoodistanal, and isoramanone. These recently discovered compounds from hoodia aid in standardizing hoodia products and serve as new research directions for potential bioactivity.

The antiobesity activity of hoodia has mostly been investigated in vivo. Different hoodia species showed a large reduction of weight in obese rats and a "moderate" reduction of weight in lean rats at an effective dose of 1.8-2.7 g/kg body weight. In general, studies showed that hoodia consumption resulted in less food intake, greater water consumption, decrease in weight gain, and weight loss in animal models. In hypothalamic neurons, incubation with P57 resulted in a 50-150% increase of adenosine triphosphate (ATP). This result was confirmed by injecting P57 into the brain's third ventricle in rats, leading to the conclusion that hoodia may work via the hypothalamus in the central nervous system among other possible mechanisms of action.

There are only a few reported clinical studies. Pharmaceutical company Phytopharm observed the reduction of caloric consumption by 1,000 calories, approximately 2 kg of weight loss, and corresponding positive effects on blood glucose and triglycerides when consuming hoodia extract in a placebo-controlled, double-blind study with 20 obese patients. In a 4-week study of a product claimed to contain 400 mg of raw hoodia in a capsule, obese patients were reported to lose 2-15 lbs and have a reduced appetite, decreased caloric consumption and carbohydrate craving, and a mild increase in energy.

Oxypregnane glycoside compounds hoodigosides A-K and P57 were found not to be cytotoxic and did not inhibit the growth of SK-MEL, KB, BT-549, SKOV-3, VERO, or LLC-PK1 cell lines at a concentration of 25 µg/ml. These compounds did not display any antioxidant activity in various tests. P57 was found to lessen aspirin-induced gastric damage by 91.5%, and 50 mg/kg of hoodia extract decreased gastric acid output by 50% and gastric emptying by 26%. However, P57 was found to completely degrade in simulated gastric fluid (SGF).

Acid or enzyme hydrolysis of P57 leads to the formation of its aglycone hoodigogenin A. Investigation of the stability of P57 in SGF for 60 minutes showed that this yielded hoodigogenin A. In contrast, hoodigogenin A was stable when incubated with SGF, and this compound was shown to have permeability in Caco-2 cells. Experimental results also predict that hoodigogenin A should be able to pass through the blood brain barrier. Studies of P57 in Caco-2 cells showed that oral bioavailability of the compound is likely affected by membrane transporter efflux. Additionally, an in vivo experiment confirmed "moderate" oral bioavailability of P57 and suggested that it is degraded in the gastric environment.

Toxicity studies on hoodia have been mixed with many of them reporting data on the use of hoodia combined with other agents. A hoodia extract fed to mice ranging from 100 mg/kg to 3028.5 mg/kg did not result in any toxicity; however, a dosage of 200 mg/kg caused reversible morphological changes to the liver of animals. No adverse side effects were reported in either the antiobesity experiments in vivo or the limited information available from clinical trials of hoodia. Traditional safe use of the whole fresh plant taken occasionally cannot necessarily be extrapolated to concentrated extracts or isolated components consumed on a daily basis for prolonged periods.

Several methods have been developed to differentiate between hoodia species and to detect adulterants. The most common technique for detecting P57 is liquid chromatography (LC). Additionally, ultra-performance liquid chromatography (UPLC), in combination with ultraviolet (UV) detection and mass spectrometry (MS), has been used to fingerprint 12 different hoodigosides in hoodia species (UPLC-MS) and quantify P57 (UPLC-UV) in hoodia products. Another successful technique is high-performance thin layer chromatography (HPTLC). This has also been used to differentiate hoodia species as well as identify the presence of P57.

Natural products for obesity are not always either safe or effective. Toxicity studies on hoodia are still necessary to ensure safety of the consumption of large amounts of the plant. Also, the adulteration of hoodia is a significant problem and phytochemical techniques that differentiate between Hoodia species are still needed. Although P57 is well-researched, the breakdown of the compound in the gastric environment points to future research on other hoodia compounds. Lastly, additional clinical trials are necessary to confirm the use of hoodia in the treatment of obesity.   
   


La plante nommée ǁhoba ([kǁʰɔbɑ] par les Bushmans était déjà connue pour un effet au niveau de l’hypothalamus [1]. Une équipe brésilienne de neuropharmacologie de Fortaleza a cherché à savoir quel autre effet pourrait avoir l’extrait de Hoodia gordonii (Masson) Sweet ex Decne. Des souris ont été traitées par des administrations pendant 15 jours de 25 et 50 mg/kg-poids d’extrait de H. gordonii et ont été soumises au test de la nage forcée et à l’open-field test. Une administration unique de cet extrait a fait baisser l’immobilité de l’animal dans le test de nage forcée, sans modifier son activité dans l’open-field test. Cet effet positif est inhibé si les souris sont prétraitées par du PCPA (parachlorophénylalanine: inhibiteur de la synthèse de la sérotonine), du NAN-190 (antagoniste de 5-HT1A), de la ritansérine (antagoniste du 5-HT2A/2C), de l’ondansétron (antagoniste de 5-HT3A), de la prazosine (antagoniste de l’α1-adrénocepteur), du SCH23390 (antagoniste du récepteur à la dopamine D1), de la yohimbine (antagoniste de l’α2-adrénocepteur), et du sulpiride (antagoniste du D2 récepteur). Sous extrait de · on note une augmentation significative des niveaux de 5-HT dans le striatum lors d’un traitement minute, tandis que la 5-HT, la noradrénaline et la dopamine ont été significativement plus élevés dans un traitement de longue durée. La drogue pourrait donc avoir un effet antidépresseur-like de type IRS-NA (dopamine-, sérotonine- et noradrénergique) [2].


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