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South African Journal of Botany 86 (2013) 51–55

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South African Journal of Botany
journal homepage: www.elsevier.com/locate/sajb

Metabolic effect of short term administration of Hoodia gordonii, an herbal
appetite suppressant
S. Jain, S.N. Singh ⁎
Nutrition Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054, India

a r t i c l e

i n f o

Article history:
Received 5 December 2012
Received in revised form 29 January 2013
Accepted 2 February 2013
Available online 6 March 2013
Edited by AM Viljoen
Keywords:
Hoodia gordonii
Appetite
Food intake
Leptin
Ghrelin
Neuropeptide Y

a b s t r a c t
Hoodia gordonii (family: Apocynaceae) is used traditionally by the Khoi-San tribes to control hunger. It has
become extremely popular and has triggered commercial interest due to its appetite suppressant property.
The present study was undertaken to investigate the appetite regulatory mechanism and associated metabolic changes induced by the herb. Effect of organic solvent extract of H. gordonii on food intake and body weight
of male Sprague Dawley rats was monitored at three different doses 50, 100 and 150 mg/kg body weight,
given orally for five days. Subsequently, the dose of 100 mg/kg body weight was selected for further studies
on the regulatory hormones and biochemical variables. Dose-dependent reduction in food intake (12–26%)
was observed at a dose of 100 and 150 mg/kg body weight (p b 0.05). Appetite suppression persisted for
6 h and food intake was restored within 24 h after stopping of the treatment. There was an increase in
liver glycogen stores, activity of mitochondrial CPT-1 and thyroid hormones in treated animals. The circulating levels of NPY and IGF-1 were decreased with marginal increase in leptin and CCK, in case of treated rats.
There was no change in blood glucose and insulin levels were not affected significantly. The hormonal and
metabolic changes due to treatment with the H. gordonii extract may be responsible for its anorectic activity.
© 2013 SAAB. Published by Elsevier B.V. All rights reserved.

1. Introduction
There has been a global increase in the use of herbal products for
health care (Hermann and von Richter, 2012). Traditional systems
of medicine rely on herbs for their medicinal properties (Arun and
Nalini, 2002; Caili et al., 2006). Hoodia gordonii, is a popular supplement and one of the most widely consumed appetite suppressant of
natural origin. It is a succulent plant that belongs to the family
Apocynaceae and grows throughout South Africa and Namibia
(Brunys, 2005). Hoodia with the name ‘Xhoba’ have been in use by
the indigenous Khoi-San tribes of the Kalahari during their long hunting trips to curb hunger or during periods of famine. Further investigation by the Council for Scientific and Industrial Research (CSIR,
South Africa) about the genus Hoodia led to the finding that out of
the 13 reported species only H. gordonii and H. pilifera exert anorectic
activity (Avula et al., 2006). Initial studies demonstrated a decrease in
food intake and body weight in obese and lean rats (Tulp et al., 2001,
2002). It is reported that H. gordonii is a rich source of pregnane,
oxypregnane and steroidal glycosides (Shukla et al., 2009). Experiments performed by MacLean and Luo (2004) demonstrated that a
specific steroidal glycoside, P57 when administered by i.c.v injection
increases the amount of ATP in the hypothalamus, which stimulates
satiety and is indicative of a central mechanism of action. However,
a pharmacokinetic study revealed that oral administration of Hoodia
⁎ Corresponding author. Tel.: +91 1123883315.
E-mail address: nutrition-dipas@hotmail.com (S.N. Singh).

extract, does not cause an increase in P57 in brain (Madgula et al.,
2010). The precise mechanism of its action has not been elucidated.
Limited human clinical trials with H. gordonii have been done. An observational pilot research study was performed on obese participants
and effects on body weight and appetite were assessed (Holt and
Taylor, 2006). A specific product called Hoodia Supreme was administered twice daily in form of capsule that contained 400 mg of pure
H. gordonii per capsule. Reduction in appetite (500–1000 calories
per day) and weight loss (2–15 lb) were reported in all subjects
over the duration of 4 weeks (Holt and Taylor, 2006). In a double
blind, placebo controlled study, a group of obese free- feeding volunteers were treated with H. gordonii. A reduction of food intake up to
1000 calories per day (approx.) and body weight loss of about 2 kg
along with decrease in blood glucose and triglycerides was observed
(Glasl, 2009; Holt and Taylor, 2006).
A purified solvent extract, HgPE (H. gordonii purified extract)
containing 79.3% w/w steroid glycosides was formulated as a flavoured
yoghurt drink (Blom et al., 2011). This HgPE caused a significant dose
dependent reduction in food intake and body weight of rats when repeatedly administered for 13 weeks (Blom et al., 2011). This HgPE extract was also evaluated on healthy overweight women at dose of
1110 mg HgPE twice/day, 1 h before breakfast and dinner for a period
of 15 days. The placebo group was given a yoghurt drink. The mean
effects on ad libitum energy intakes and body weights did not differ
significantly between the treated and placebo groups. Inspite of the
enormous commercial interest in H. gordonii supplements, there is insufficient published scientific data on regulation of appetite. Some

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Sample collection for biochemical analysis After completion of the five day treatment. AMP kinase activity. 1b). 1e).N. Plasma leptin and adiponectin concentrations were measured with a commercially available rat ELISA kit from Ray Biotech. Tissue glycogen was estimated using the method of Montgomery (1957). Farm Douglas.e.000 ×g for 30 min at 4 °C and stored at −80 °C for CPT-1 activity analysis. 3. S. There was no change in food intake at a lower dose of 50 mg/kg body weight (Table 1). Namibia. At 150 mg the rate of body weight gain in treated rats was 1. Statistical analysis All the data are presented as mean ± SD and statistically analyzed using unpaired Student's t-test. treatment. 2. The weight of the organs — liver. gordonii crude extract at oral dose of 100 mg/kg and 150 mg/kg produced a dose-dependent decrease in food intake over the 6 h period on all the five days.4. Extraction was repeated twice under identical conditions. There was a decrease in food intake by 17. Rats were habituated to a restricted day-time feeding regimen two weeks prior to the experimentation by providing them food only for 6 h during the light phase for monitoring of food intake. CPT-1 (Carnitine Palmitoyl Transferase-1) activity was assayed using the method of Halperin and Pande (1979).8% as compared to 6% in control indicating a reduction in weight gain due to treatment (Fig.8%) compared to control (3. CA were used for detection of plasma ghrelin.1.3.5% (12. The supernatants were divided into aliquots and frozen at −80 °C until assayed.2. its possible effects on energy metabolism and other biochemical changes using young adult Sprague Dawley rats as an experimental model. 2. All procedures and protocols used in the present study were approved by the Animal Care and Use Committee of the Institute and followed the guidelines documented in the National Institute of Health's Guide for the Care and Use of Laboratory Animals.4%–26. bred and reared in the Experimental Animal Facility of the Institute were used in the study. Plasma insulin concentrations were determined using a direct ELISA kit bought from Mercodia. at the time of providing food and water to the animals.5. precipitated with 95% ethanol in the presence of sodium sulphate. Food was weighed on a digital balance every 2 h i. The yield of the extract was 8. The respective control groups for each treatment group received equal volume of tap water using a rodent feeding needle. 1d). Singh / South African Journal of Botany 86 (2013) 51–55 researchers have confirmed the appetite suppressing property of Hoodia species but there are no reports on its effect on the appetite regulatory peptides. For glycogen estimation the weighed portions of liver were dissolved in 30% KOH immediately after removal. Changes in body weight were monitored daily post treatment.8% (18. Delhi and water ad libitum.0% of the dry powder supplied by the manufacturer. The p value b 0. control and treated (n = 6 in each). rats were fasted overnight.. levels of tri-iodothyronine (T3). weighing 200–250 g. Certificate of Analysis along with the LCMS chromatogram for H. The minimum effective dose of 100 mg/kg body weight was selected subsequently for further biochemical experiments. Preparation of extract Organic solvent extract was prepared using a mixture of dichloromethane-methanol (1:1) (Corley and Miller. 2 h and 4 h after giving an oral dose of 100 mg/kg body weight (n= 6).1. Animals. The animals were randomly divided into control and experimental groups prior to the beginning of the experiments. body weight and organ weights H. Effect on food intake. Initially six groups of animals (n = 6 in each) were treated with crude alcoholic extract at doses of 50. Ltd. 2. This indicates that the extract has a transient action and not a sustained effect. No significant differences in the weights .52 S. USA. lights off at 18:30 h). samples were collected from the retro-orbital plexus at 1 h. gordonii was a gift from M/S Farm Vredelus PTY LTD. The organic layer was separated from raw plant material by centrifugation at 3000 ×g for 15 min at room temperature.05) (Table 1). gordonii. anaesthetized and sacrificed. Mitochondrial protein content was measured by the method of Lowry et al.1. Results and discussion 3. Animals were maintained at a temperature of 22° ±1 °C and a humidity of 55–60% in light-controlled room (lights on at 6:30 h.. (1951).7%) compared to control (4%) (Fig. at dose of 100 mg/kg body weight there was no significant effect on body weight in treated animals (3. The body weight was not affected in the treated animals (3. the study was undertaken to further investigate the acclaimed anorectic activity of H. supernatants were combined and dried at 40 °C. 05 was considered significant change. Radio immunologic assay (RIA) kits from Phoenix Pharmaceuticals. thyroxine (T4) and 5-Hydroxytryptamine (5-HT) in brain homogenates and plasma were measured using kit from Cusabio biotech Co. In a separate experiment to study the effect on blood glucose levels. Rats were provided commercial rodent diet supplied by M/S Golden feed Pvt Ltd. 2. Jain. Ten percent liver and brain homogenates (w/v) were prepared in 150 mm KCl using Polytron homogeniser and were centrifuged at 3000 ×g for 15 min at 4 °C. spleen.6%) at the dose of 50 mg/kg body weight (Fig. Materials and methods 2. Similarly. monitoring of food intake and body weight Male Sprague Dawley rats.1. The extract was given in the morning every day for five days.. kidney. 100 and 150 mg/kg body weight orally using a rodent feeding needle once daily for five days.3%) and 22. Inc. Biochemical estimations Blood glucose was measured using glucose oxidase–peroxidase method. 2. USA). Liver mitochondria were separated by differential centrifugation at 12. 2009). The food intake returned to the levels of untreated group from day 6 to day 8 after the 100 mg/kg body weight dose was discontinued on day 5 (Fig. South Africa). Sweden. Na+/K+ATPase activity was measured in the brain homogenate using the method of Esmann (1988). Germany. In the experiment carried out to monitor food intake at different time points a reduction in food intake by 15% was observed at 2 h following administration and remained up to the sixth hour (Fig.7%) respectively at dosage of 100 and 150 mg/kg body weight (pb 0. 4 h and 6 h to see if the extract has a continuous or progressive anorectic action. Based on this.4%–22. Plasma samples were extracted using ethyl ether for corticosterone estimation and estimated using an ELISA kit (Neogen Corporation. 1a). This was performed on a separate batch of rats comprising of two groups. 2. neuropeptide Y (NPY) and cholecystokinin (CCK) levels. at 2 h. Uppsala. Dry powder was weighed (20 g) and mixed with a 100 ml solvent mixture and kept overnight for extraction. Blood plasma was collected by centrifugation at 1000 ×g for 10 min at 4 °C. Food intake was monitored additionally for three days (over an eight day period) to find out any residual effect after stopping the treatment. Plasma levels of insulin-like growth factor 1 (IGF-1) were analyzed with an EIA kit from Mediagnost. brain was recorded along with gastrocnemius muscle and epididymal fat tissue. gordonii were also provided by them (LC/MS analysis was done at University of Stellenbosch. Burlingame. 1c). Plant material Authenticated dry powder of (cultivated) H.

4 80. (b) Recovery in food intake after stopping treatment with 100 mg/kg body weight (n=6).04 97 85 −12 12.3 97.2 ± 2. T: Treated. (e) Changes in body weight of rats following H.4 96.8 ± 4.3 −18.2 95. (c) Changes in body weight of rats following H. pure glycoside or a formulated product.6 22.4 97.5 24.7 100 81.7 22.4 97 74. 2007. + denotes an increase and − denotes a decrease in food intake in comparison to control. 53 of vital organs and epididymal fat tissues were found between the groups (data not shown). 2001). Human trial with H.0 101. Fig.8 99 78 −21 21. The recovery in food intake after stopping the treatment is also reported in an earlier study by van Heerden et al.8 ± 1. S. However.8* Values are mean ± SD (n = 6).9 −0.7 ± 2.6 100 150 C (g) T (g) Diff (g) Diff (%) C (g) T (g) Diff (g) Diff (%) C (g) T (g) Diff (g) Diff (%) 98. (2007). (d) Changes in body weight of rats following H.0 +1 1.0 97. the dosage and the extent to which food consumption was suppressed varied.N.2 ± 3.. gordonii administration at dose of 100 mg/kg body weight (n=6).0 +1 1 101 84 −17 16. Singh / South African Journal of Botany 86 (2013) 51–55 Table 1 Effect of crude H. (a) Effect of H.6 99. 1.5 −22. The decrease in food intake and reduction in weight gain in the treated groups in the present study indicates appetite suppression in rats and this observation is similar to earlier reports (van Heerden et al.4 74.5* 97. 2011)..1 ± 2. Oral treatment (mg/kg body weight) Day 1 Day 2 Day 3 Day 4 Day 5 Mean ± SD 50 96.0 +1 1 97 75.6 71. gordonii extract on food intake..1 26.7 97.0 17. C: Control.S. Tulp et al. gordonii showed reductions in food intake and body weight from baseline but with no significant difference between the experimental and placebo groups (Blom et al.7 ± 2 0. 2004. gordonii administration at dose of 50 mg/kg body weight (n=6). Jain. the form of the herb used i. Holt (2005) quotes H.2 100.0 0 0 95 78.4 −21.0 100.5 17.05. *p b 0.7 95 77.5 72 −23.5 18. gordonii is not a ‘magic bullet’ for overweight problems but imperatively modifies food behavior and thereby leads to the controlled energy intake.0 94. gordonii administration at dose of 150 mg/kg body weight (n=6).e.4 95.0 96.5 23.1 2.7 18. . This could be due to the complex interactions between the biological mechanisms of appetite and environmental challenges that determine drive to eat.5 −16.5 ± 0.5 −26. combined food intake of 6 rats.5 −17. MacLean and Luo.0 ± 2. gordonii treatment on food intake at specific time points for 6 h at dose 100 mg/kg body weight (n=6).

2010). HG: 292. HG: 0. CPT-1 activity in the isolated liver mitochondria was found to be significantly increased in the treated group (control: 10. 2007).05) in the present study may be in response to the lower calorie intake. were found to be significantly decreased (pb 0. Effect on enzyme activities The gastrointestinal tract and the adipose tissue both send signals to the brain and regulate the energy homeostasis (Stanley et al. Low IGF-1 levels are seen in fasting and are increased in response to high calorie intakes (Sridhar and Goodwin. It could have a role in lipolysis. 2006).81 ± 4.. a single molecule can have several metabolic effects (Tucci. though its function in lipid regulation is complicated (Mariash.019 ± 0. In the present study changes in levels of appetite regulatory peptides in response to H. 2004). The significantly increased activity of CPT-1. gordonii supplementation in vivo may be responsible for decreased food intake. The NPY/AgRP neurons play an important role as they mediate the effect of ghrelin (Cowley et al. it may also have a peripheral action (MacLean and Luo. 1999). an enzyme of the fatty acid oxidation. may be in part attributed to the raised adiponectin in the present study. Tucci. 2006). but only recently it's been known to act centrally as well (Amin et al. leptin inhibits NPY (Baskin et al. This could lead to an assumption of elevated basal energy expenditure arising from increased fuel metabolism (Pucci et al. which is yet to be proven. 2004).05) and leptin levels show a similar association in the present study. thyroid hormones promotes carbohydrate metabolism and maintains glucose homeostasis (Chidakel et al.02 mmol/mg protein/min).. it appears that adiponectin did not exert its effect peripherally to stimulate the liver AMP kinase activity.. Both serotonin and corticosterone in rodents have the highest peak during the active period of the diurnal cycle.97 ± 9. 2010) the activity of Na +/K +ATPase was measured in whole brain and no change was observed (control: 0.50 μmol/min/mg protein. HG: 16. no food restriction during the experiment was done. though values were statistically not significant. 3. 1992). 2003) and since leptin receptors are present on these neurons. However. In the present study circulating levels of corticosterone. 2004).. Additionally the appetite and metabolic rate are controlled through the peripheral effects of thyroid hormone that have clinical significance on energy intake.. These effects were thought to be peripheral. gordonii on serotonin levels were observed. Insulin is known to increase the production of IGF-1 (Butler and LeRoith. 2003). 3. 2.54 S. It has been suggested that the effects of Hoodia on blood glucose and insulin are not direct. gordonii resembles the structure of cardiac glycosides (MacLean and Luo. However. The levels of glucose and glycogen in the treated group may be mediated to a certain extent by the increased thyroid hormones (Table 2)..75 mg/g wet tissue. Insulin regulates glucose homeostasis by increasing glucose uptake.2.77 ± 0.54 μmol/min/mg protein. The 5-HT is a suggestive satiety agent (Fernstrom and Fernstrom. Therefore possibility of serotonin reuptake inhibition remains unidentified and needs further study. Jain. A marginal increase in CCK secretion was also noted. 2009). Also. Since the steroidal glycoside. The insulin levels did not show any significant change in the present study. The blood glucose concentration signals the induction of hunger sensation in rats (Poothullil. 2005). Although the herb is postulated to alter appetite through the CNS.. HG: 1. since some cellular receptors tend to be widely distributed.05) in the treated group. A decline in ghrelin levels has an appetite lowering effect while leptin decline has appetite stimulating effects. Effect on blood glucose and liver glycogen The blood glucose levels were not affected by treatment at 1 h. T3 and T4 displayed a significant rise (pb 0. P57 present in H. 2009). and may occur only when on a calorie reduced diet or in combination with cinnamon and anti-hyperglycaemic compounds to treat Syndrome X (Holt. no ATP depletion resulting in a feeling of satiety (MacLean and Luo.05). there was a significant increase (p b 0. In the present study an increase in leptin and concomitant suppression in ghrelin levels. CCK is known to be a peripheral gastrointestinal satiety signal. p b 0..3. The decline in the plasma IGF-1 levels (p b 0. S..72 mg/g wet tissue).. 2000). Effect on blood glucose levels measured at 1 h. p b 0. 2003). No significant effect of H. This implies that if given for a longer period it may exert a pronounced effect. 2001). as a no significant change in the AMPK activity could be due to Fig.4. This is achieved by stimulating the glucoreceptors that sends satiety signals to the brain via the vagus nerve (Anderson. Singh / South African Journal of Botany 86 (2013) 51–55 3.05) while the AMPK activity measured in crude liver homogenates was not changed with HG supplementation (control: 314 ± 54 pg/mg protein.46 ± 0. Depleting Adenosine triphosphate (ATP) or increasing Adenosine monophosphate (AMP) levels activates AMPK (Shetty et al. and the fall of blood glucose is a stimulus for increased appetite.N. 2 h and 4 h post intervention (Fig.. 2011). thereby not increasing food intake (Kubota et al. those of the light period. The increase in liver glycogen is probably related to a change in sugar metabolism through the glycosides present in Hoodia (Holt. Plasma ghrelin concentrations are known to correlate with calories ingested (Cummings et al. 2001). This reinforces the observation. 2 h and 4 h after H. Effect on appetite regulatory peptides Plant extracts usually target several systems of the body as majority of them are not single compounds but a mixture of different molecules. However.05) after the supplementation. 1994). 2005). Traditional belief that herbs are safer than synthetic compounds is one of the classical arguments.18 pg/mg protein. the role of monoamines in eating has also been observed. it is difficult to pin point any one molecule responsible for the action as appetite regulation is a complex phenomenon and plant extract used may have several compounds other than P57. A decline in both of these peptides in this study may also have a role in appetite suppression. The significant decrease in plasma NPY (pb 0. 2010). this may affect lipid metabolism and enhances fatty acid oxidation (Xu et al.01 mmol/mg protein/min. ghrelin and IGF-1 closely affect the nutritional status.73 ± 6.01) in the hepatic glycogen content (control: 0. Increased glycogen production leads to an early feeling of fullness. 2001). 2).. Food intake and the appetite hormone systems like leptin. gordonii supplementation at 100 mg/kg body weight (n=6). 2004. Glucocorticoids stimulate food intake by promoting NPY functions (Woods et al. gordonii may lead to secretion of CCK and influence appetite control (Le Nevé et al. The short term administration of the crude extract generates adequate evidence of it being an appetite suppressant.018 ± 0. Recent research has proposed that the bitter taste of H. The extensive . Besides. Apart from neuropeptides.

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DIPAS for encouragement and support to the study... Vleggaar.A. Monoamines and protein intake: are control mechanisms designed to monitor a threshold intake or a set point? Nutrition Reviews 59. Adiponectin in health and disease: evaluation of adiponectin-targeted drug development strategies.. An appetite suppressant from Hoodia species. Li.D. Ueki. Pawar. Schweizerische Zeitschrift für Ganzheitsmedizin 21..... Mariash. 1171–1181. Sugi. Pharmaceuticals 3.F.E. 675–683. J. overweight women: a randomized controlled trial. Yamauchi. 2005. 2007. T. Liu..16 56. Araki.. Farr. K.. L.. K Verma in animal handling is gratefully acknowledged. 524–536. Present investigation on experimental animals needs further studies on humans since the feeding behaviour of humans and rodents are different. Pucci. C.12* 956. L. Archives of Biochemistry and Biophysics 67. B. Gouka. Y. Planta Medica 78. Pande.V. Source of funding This study was supported from DIPAS.. Woods..C. 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