Oxypregnane glycoside

Oxypregnane Glycosides: A Comprehensive Reference

1. Identity and Chemical Classification

Oxypregnane glycosides are a structurally defined subclass of pregnane glycosides — steroidal secondary metabolites whose aglycone (steroid nucleus) is a C₂₁ pregnane skeleton bearing one or more oxygen-containing substituents. Polyoxypregnane glycosides typically carry two or more oxygen-containing substituents in the C-ring, with positions C-10, C-11, C-12, C-15, and C-20 most frequently involved. Polyhydroxy pregnane glycosides usually contain three or more hydroxyl groups, most frequently at C-5, C-8, C-14, C-16, and C-17; 17-furan pregnane glycosides can be divided into seco- and diseco-types based on the connectivity at C-17; and bidesmoside-type pregnane glycosides possess oligosaccharide chains at both C-3 and C-20 of the aglycone.

The best-characterized individual oxypregnane glycoside in the scientific literature is P57AS3 (commonly abbreviated as P57), isolated from Hoodia gordonii. P57AS3 was found to have structural homologies to the steroidal core of cardiac glycosides. The predominant aglycone present across the majority of Hoodia oxypregnane glycosides is known as hoodigogenin A. Hoodigosides A–K share a common aglycone moiety: 12-O-β-tigloyl-3β,14β-dihydroxypregn-5-en-20-one (hoodigogenin). Additional aglycone chemotypes isolated from Hoodia gordonii include isoramanone, calogenin, hoodistanal, and dehydrohoodistanal.

Because of the diverse structures and excellent biological activities of pregnane glycosides, considerable synthetic work has been undertaken for the construction of their core structures, although few studies have reported the total synthesis of pregnane glycosides.

2. Botanical Sources and Natural Distribution

Oxypregnane glycosides are naturally occurring compounds predominantly found in certain plant species, especially within the Asclepiadaceae family, such as Hoodia gordonii and Caralluma fimbriata. Current taxonomy places many former Asclepiadaceae members within the broader family Apocynaceae. Pregnane glycosides are found in Asclepiadaceae, Apocynaceae, Malpighiaceae, Ranunculaceae, and Zygophyllaceae; natural pregnane glycosides are mainly distributed in the genera Caralluma and Cynanchum of Asclepiadaceae, and these plants mainly grow in arid areas such as India, Arabia, and southwest China.

Key Source Plants

• Hoodia gordonii (Masson) Sweet ex Decne. (family Apocynaceae): A succulent plant found wild in the Kalahari deserts of South Africa, Namibia, and Botswana. Eleven new oxypregnane glycosides (hoodigosides A–K) and the previously reported oxypregnane glycoside P57AS3 have been isolated from the aerial parts of H. gordonii.
• Caralluma fimbriata Wall. (family Apocynaceae/Asclepiadaceae): An Indian herb widely used for obesity in traditional medicine; an edible succulent cacti belonging to the Asclepiadaceae family, well-known as a famine food and appetite suppressant, growing wild all over India.
• Caralluma penicillata: The chloroform fraction of the defatted ethanol extract from the aerial parts of Caralluma penicillata yielded three C-15 oxypregnane glycosides, the penicillosides A–C. Oxypregnane glycosides, the penicillosides D–G, have also been identified in the aerial parts of this species.
• Cynanchum auriculatum Royle ex Wight: In the search for plant alternatives to Hoodia gordonii containing P57, the roots of Cynanchum auriculatum were investigated, yielding 15 pregnane glycosides, of which nine were never previously reported. Two new cytotoxic pregnane glycosides, kidjoranin 3-O-α-diginopyranosyl-(1→4)-β-cymaropyranoside and kidjoranin 3-O-β-digitoxopyranoside, together with caudatin 3-O-β-cymaropyranoside, have been isolated from its roots.
• Gymnema sylvestre (Retz.) R.Br.: A medicinal plant used in Indian Ayurvedic traditional medicine for the treatment of diabetes; phytochemical investigation has led to the isolation of five new pregnane glycosides, gymsylosides A–E.
• Cynanchum marnierianum and related Cynanchum species: The ethanolic extract of Cynanchum marnierianum yielded two new pregnane glycosides named marnieranosides A and B, which present structural analogies to pregnanes previously described in species known for their appetite suppressant and antihyperglycemic effects, such as P57 from Hoodia gordonii.

3. Traditional and Historical Use

Southern Africa: The San (Khoisan) People

Hoodia gordonii is a succulent plant consumed by the Bushmen in South Africa to reduce appetite, and its proposed active compound for weight loss, P57, is an oxypregnane glycoside. Many books and articles have documented the use of stapeliad species (the plant group to which Hoodia belongs) as food plants, with earlier references relating to the use of Hoodia species as a thirst quencher; however, prior to the publication of the patent application, only a single reference referring to the use of Hoodia pilifera as an appetite suppressant was found in the scientific literature. This reflects the predominantly oral and undocumented nature of indigenous ethnobotanical knowledge for this species.

India: Tribal and Ayurvedic Traditions

Indian tribal people have used Caralluma fimbriata as a natural appetite suppressant for many centuries, and in times of famine it has been a commonly used vegetable. Traditionally, Indian tribes chewed chunks of Caralluma to keep from being hungry during a long hunt; these days a solution containing chemicals extracted from the plant is used to decrease appetite for weight loss, and it has also been used to quench thirst and increase endurance.

Various medicinal uses of Caralluma species have been documented in Arabic and Indian traditional medicine, including treatment of diabetes, cancer, tuberculosis, snake and scorpion bites, skin rashes, scabies, fever, and inflammation; the most common use of this genus recorded has been as a famine food without any reported adverse effects.

In traditional Indian food culture, Caralluma fimbriata is part of many traditional Indian diets, eaten raw or boiled and often combined with vegetables and spices, and also used in preserves like chutney and pickles.

Gymnema sylvestre is renowned in Ayurvedic medicine for its role in supporting healthy glucose metabolism, earning it the moniker "sugar destroyer." The pregnane glycosides isolated from this plant have more recently been the focus of scientific investigation for their glycosidase-inhibitory activity.

4. Key Constituents and Active Compounds

Multiple individual oxypregnane glycosides have been isolated and characterized from various botanical sources. Phytochemical study of Hoodia gordonii aerial parts has led to isolation of seven pregnane glycosides (hoodigosides W–Z, hoodistanalosides A–B); their structures were elucidated by chemical degradation studies and spectroscopic methods, including 1D and 2D NMR and CD spectroscopic methods.

In total, phytochemical studies on H. gordonii have reported the isolation and characterization of 11 new oxypregnane glycosides (hoodigosides A–K) and 10 new calogenin glycosides (hoodigosides L–U). These compounds were used as markers for developing HPLC and LC–MS based methods for the identification and quality control of H. gordonii plant materials and dietary supplements.

In Caralluma species, pregnane glycosides isolated and identified from African Hoodia are reported as anti-obesity and appetite-suppressant compounds; on reviewing the studies on chemistry, pharmacology, and therapeutic potential of Caralluma, it is concluded that the genus also contains pregnane glycosides as one of its major constituents, which is considered an indication of its appetite-suppressant property.

A structurally distinctive feature of many oxypregnane glycosides is their sugar moieties. Pregnane glycosides from Hoodia are characterized by an aglycone (either hoodigogenin A or calogenin) and sugar side chains structured by different 6-deoxy and/or 2,6-dideoxyhexopyranose moieties.

In Gymnema sylvestre, all isolated pregnane glycoside compounds were evaluated for their α-glucosidase and α-amylase inhibitory activities; compounds 2–4 showed significant α-amylase inhibitory activity, with IC₅₀ values ranging from 113.0 to 176.2 µM.

5. Established Mechanisms of Action

Hypothalamic ATP Elevation (Satiety Signaling)

The most extensively studied mechanism for oxypregnane glycosides relates to the compound P57AS3 and the hypothalamic energy-sensing pathway. P57AS3 was isolated from Hoodia gordonii and found to have homologies to the steroidal core of cardiac glycosides; intracerebroventricular (i.c.v.) injections of the purified P57AS3 demonstrated that the compound has a likely central (CNS) mechanism of action; there is no evidence of P57AS3 binding to or altering the activity of known receptors or proteins, including Na/K-ATPase, the putative target of cardiac glycosides; and the studies demonstrated that the compound increases the content of ATP by 50–150% in hypothalamic neurons.

The studies demonstrated that the compound increases the content of ATP by 50–150% in hypothalamic neurons; in addition, third-ventricle (i.c.v.) administration of P57, which reduces subsequent 24-h food intake by 40–60%, also increases ATP content in hypothalamic slice punches removed at 24 h following the i.c.v. injections.

With growing evidence of metabolic or nutrient-sensing by the hypothalamus, ATP may be a common currency of energy sensing, which in turn may trigger the appropriate neural, endocrine, and appetitive responses, similar to other fundamental hypothalamic homeostatic centers for temperature and osmolarity.

Important limitation: The proposed active compound for weight loss, P57, was shown to cause increased ATP production in the hypothalamus after intracerebroventricular administration; however, this mechanism of action is debatable, as there was no detectable P57 in the brain after oral administration in CD1 female mice. This finding calls into question whether oral administration of oxypregnane glycosides achieves the concentrations at the hypothalamus necessary to replicate the animal injection studies.

Downregulation of Ghrelin and Neuropeptide Y

One hypothesis is that Caralluma fimbriata may down-regulate ghrelin synthesis in the stomach and neuropeptide-Y in the hypothalamus, resulting in appetite suppression. Pregnane glycosides in Caralluma fimbriata extract (CFE) are most likely responsible for this effect, through their action on the hypothalamus and the cortisol response.

GLP-1 Secretagogue Activity

In the framework of the search for natural glucagon-like peptide-1 (GLP-1) secretagogues, bioassay-guided fractionation of the ethanolic extract from Cynanchum marnierianum led to the isolation of two new pregnane glycosides. Pregnane glycosides at 70 µM have been shown to stimulate secretion of GLP-1 in the STC-1 murine intestinal neuroendocrine cell line, hinting at a role in regulation of appetite. This mechanism is preliminary and based on in vitro data only.

Inhibition of Fat Synthesis Enzymes

Several pregnane esters and glycosides isolated from plants are credited with observed activities including hunger suppression and inhibition of the sensory mechanisms of the hypothalamus; one proposed mechanism is obstruction of the creation of acetyl co-enzyme A and malonyl co-enzyme A, which are basic components of fat synthesis.

Leptin Sensitivity

Members of the family Apocynaceae, such as Caralluma spp. and Hoodia spp., contain pregnane glycosides that have been shown to restore sensitivity to the appetite suppressant hormone leptin in obese mice. This finding is from animal studies only.

Enzyme Inhibition (Glycosidase Activity)

All isolated pregnane glycosides from Gymnema sylvestre were evaluated for their α-glucosidase and α-amylase inhibitory activities; compounds 2–4 showed significant α-amylase inhibitory activity with IC₅₀ values ranging from 113.0 to 176.2 µM. These results are in vitro and have not been confirmed in human clinical trials specific to oxypregnane glycosides from this source.

6. Scientific Evidence by Area of Use

6.1 Appetite Suppression and Weight Management

Hoodia gordonii — Human Clinical Evidence

Only one small study has been done on the effects of hoodia supplements in people; that study involved 49 women who were overweight, and those who took hoodia for 15 days did not lose more weight than those who took a placebo. This study was published in the American Journal of Clinical Nutrition (Blom et al., 2011). Healthy, overweight women were stratified by percentage body fat and received either HgPE (n = 25) or a placebo (n = 24) for 15 days; subjects were resident in a clinic for a 4-day run-in period and a 15-day treatment period, receiving 2 servings/day of 1110 mg HgPE or a placebo formulated in a yogurt drink 1 hour before breakfast and dinner.

Although controversial appetite-suppressant effects have been demonstrated in some in vivo experiments conducted on rats and chickens, human evidence is still lacking; the only available human clinical study reported no change in body weight or energy expenditure, and administration of a purified H. gordonii extract was associated with a significant increase in blood pressure and pulse rate.

The NCCIH summarizes the state of evidence: it is thought that P57, an oxypregnane steroidal glycoside found in hoodia, could have an appetite-reducing effect, and today hoodia supplements are promoted for appetite suppression and weight loss; however, very little is known about hoodia. Hoodia products have been marketed worldwide for weight loss; however, there is little published clinical evidence to support this application, and concerns exist regarding adverse effects; antiviral and antioxidant properties have been noted in vitro, and antidepressant activity has been demonstrated in rodents; clinical trial data are lacking to recommend the use of hoodia for any indication.

Caralluma fimbriata — Human Clinical Evidence

The earliest published randomized clinical trial in humans was conducted in India. The effect of Caralluma extract was assessed in overweight individuals by a placebo-controlled randomized trial; fifty adult men and women (25–60 years) with a BMI greater than 25 kg/m² were randomly assigned into a placebo or experimental group, the latter receiving 1 g of Caralluma extract per day for 60 days; all subjects were given standard advice regarding a weight-reducing diet and physical activity; at the end of 30 and 60 days of intervention, blood glucose and lipids, anthropometric measurements, dietary intake, and assessment of appetite were assessed.

A subsequent Australian randomized controlled trial (Astell et al., 2013) was a pilot study. In this pilot study, the effect of Caralluma fimbriata extract in combination with controlled dietary intake and physical activity on risk factors for metabolic syndrome was assessed in overweight and obese Australian subjects; this was a randomised, double-blind, placebo-controlled clinical trial in which 43 adults aged 29–59 years were recruited; the eligibility criteria included a BMI >25 kg/m² or a waist circumference >94 cm (male), >80 cm (female); 33 participants completed the 12-week study; participants were randomly assigned into two groups and received C. fimbriata extract or placebo as 500 mg capsules twice daily (1 g/day).

A further Indian randomized trial (Arora et al., 2015) showed neutral results. A total of 89 patients were randomized into a treatment group (n = 47) and placebo group (n = 42) to receive either CFE in capsule form at 500 mg b.d. for 12 weeks or matching placebo; patients were evaluated clinically and biochemically at 4, 8, and 12 weeks; at the end of the study period, both CFE and placebo for 12 weeks caused only numerical reduction in weight, BMI, waist circumference, hip circumference, and waist-hip ratio in overweight and obese individuals. A commercially available extract of CFE in an oral dose of 1 g/day claimed to have anti-obesity effects failed to yield any positive results on anthropometry.

A more recent Australian double-blind RCT (2021) recruited a larger sample. This double-blind, randomised, placebo-controlled trial examined the effect of a Caralluma fimbriata extract on biomarkers of satiety and body composition in overweight adults; eighty-three men and women aged 20–50 years completed 16 weeks of daily supplementation with either CFE or placebo; plasma cardiometabolic (lipid profile, glucose, insulin) and satiety (ghrelin, leptin, neuropeptide Y) biomarkers, body composition, diet history, and gastrointestinal function were assessed at baseline, weeks 4, 8, 12, and 16. Participants randomised to the CFE group received capsules containing 500 mg of CFE, whereas the placebo group received capsules containing 500 mg of maltodextrin. Plasma leptin concentration significantly increased at week 16 in the placebo group compared to the CFE group, which remained constant (p < 0.05). No differences were seen between the CFE and placebo groups for plasma ghrelin at baseline or at week 16; serotonin, CCK, IGF-1, or liver function test concentrations also showed no significant changes.

Overall evidence strength for appetite/weight outcomes: The body of clinical evidence for oxypregnane glycoside-containing extracts on appetite and weight is limited, with results that are mixed to negative in the most rigorously controlled trials. Hoodia gordonii is widely used as an ingredient in many food supplements despite the fact that supporting scientific evidence is scarce. The scan of literature reveals few studies regarding the efficacy and safety of C. fimbriata in humans for the management of obesity, and whatever data is available is equivocal.

6.2 Blood Glucose Regulation and Antidiabetic Activity

Various medicinal uses of Caralluma species have been documented in Arabic and Indian traditional medicine, including the treatment of diabetes. At the biochemical level, Gymnema sylvestre, a medicinal plant used in Indian Ayurvedic traditional medicine for the treatment of diabetes, has yielded five new pregnane glycosides (gymsylosides A–E) on phytochemical investigation. All isolated compounds were evaluated for their α-glucosidase and α-amylase inhibitory activities; compounds 2–4 showed significant α-amylase inhibitory activity, with IC₅₀ values ranging from 113.0 to 176.2 µM. These results are in vitro and do not yet have supporting human RCT evidence specific to oxypregnane glycosides.

The postulated mechanism of action for appetite suppression by P57AS3 is by increasing the ATP content in hypothalamic neurons that regulate food intake; additionally, H. gordonii is also patented for antidiabetic activity. The antidiabetic patent reflects preclinical interest rather than established clinical efficacy.

6.3 Cytotoxic and Anticancer Activity (In Vitro)

Two new pregnane glycosides and one known compound isolated from Cynanchum auriculatum roots were tested for their in vitro inhibitory activity against human tumor cell lines SMMC-7721, HeLa, and MCF7; all of them displayed marked cytotoxic activities against SMMC-7721 and HeLa cells with IC₅₀ values ranging from 8.6 µM to 58.5 µM, yet no activity against the MCF7 cell line was detected. These are purely in vitro findings and have not been extended to human clinical studies.

6.4 Anxiety and Stress (Preliminary Human Data)

One study (Griggs et al., 2015) found CFE effective in the management of Prader-Willi syndrome, reducing hyperphagia; an 8-week double-blind randomized clinical trial administered 500 mg b.d. CFE (n = 49) or 500 mg b.d. placebo (n = 48) to 97 adults self-reporting mild to moderate anxiety; anxiety and stress were measured at baseline, week 4, and week 8 using the GAD-7, Perceived Stress Scale, Positive and Negative Affect Schedule, and salivary cortisol. These findings are preliminary and have not been replicated in large-scale trials.

6.5 Anti-inflammatory and Antimicrobial Activities (Preclinical)

Several species of the genus Caralluma are rich in pregnane glycosides, flavone and megastigmane glycosides, and various esters, which are associated with antioxidant, anticancer, antidiabetic, anti-inflammatory, antimicrobial, anti-eczemic, antimalarial, and antifungal properties of various Caralluma extracts. Investigations of Caralluma species have revealed anti-fungal, anti-bacterial, anti-parasitic, anti-hyperglycemic, anti-gastric ulcer, cyto-protective, anti-nociceptive, anti-inflammatory, anti-oxidant, anti-trypanosomal, and anti-plasmodial activities. All these data are from preclinical (in vitro and animal) studies; no confirmatory human clinical trials exist for these specific endpoints related to oxypregnane glycosides.

7. Body Systems and Health Areas of Association

• Central Nervous System / Hypothalamus: Appetite regulation via hypothalamic ATP elevation (animal and in vitro evidence; human translation unconfirmed).
• Gastrointestinal / Endocrine: Potential ghrelin suppression, GLP-1 secretion stimulation, neuropeptide-Y modulation (in vitro and animal data).
• Metabolic / Adipose: Proposed inhibition of fatty acid synthesis enzymes (acetyl-CoA and malonyl-CoA pathways); preliminary human evidence on waist circumference.
• Cardiovascular: Observed adverse cardiovascular signals (elevated blood pressure and pulse rate) in the one available human study of Hoodia gordonii purified extract; sympathomimetic activity explored in isolated organ studies.
• Oncology (preclinical only): Cytotoxic activity against human tumor cell lines in vitro from Cynanchum-derived glycosides.
• Endocrine/Diabetic: α-Amylase and α-glucosidase inhibition in vitro from Gymnema sylvestre pregnane glycosides; traditional antidiabetic use documented.

8. Dosage Forms and Reported Dosages

Oxypregnane glycosides are not administered as isolated pure compounds in commercial dietary supplements; they are delivered via standardized plant extracts. The following dosages have been reported in published studies:

• Hoodia gordonii purified extract (HgPE): Healthy, overweight women received 2 servings/day of 1110 mg HgPE formulated in a yogurt drink 1 hour before breakfast and dinner (total 2220 mg/day) for 15 days in the one available human RCT.
• Caralluma fimbriata extract (CFE) — 500 mg twice daily (1 g/day): This dose was used in multiple studies. In one randomized trial, 89 patients received CFE in the form of capsules at 500 mg b.d. for 12 weeks. In a 16-week Australian RCT, participants received capsules containing 500 mg of CFE twice daily.
• Caralluma fimbriata extract — 1 g/day for 60 days: In the foundational Indian trial, overweight adults (25–60 years, BMI >25 kg/m²) received 1 g of Caralluma extract per day for 60 days.
• Anxiety/stress trial: In an 8-week double-blind RCT, 97 adults received 500 mg b.d. of CFE or placebo.
• Animal pharmacokinetic dose (P57): Bioavailability and pharmacokinetics of P57 were determined in CD1 female mice after administration of a single dose of enriched methanolic extract of H. gordonii (equivalent to a dose of 25 mg of P57/kg) by oral gavage or a single dose of purified P57 (25 mg/kg) intravenously.

Clinical trial data are lacking to recommend the use of hoodia for any indication; information is lacking and neither an effective nor safe dose has been established. For Caralluma, the most commonly studied dose in clinical trials is 1 g/day (as two 500 mg capsules of standardized extract).

Regarding commercially available dosage forms, various sample matrices of Hoodia-based products have been successfully analyzed in quality-control studies, including gels, capsules, tablets, sprays, tea bags, snack bars, powders, and juices.

9. Pharmacokinetics and Bioavailability

Pharmacokinetic data for oxypregnane glycosides in humans are not available. The existing data derive from animal and in vitro studies.

After oral administration of Hoodia extract to CD1 female mice (dose equivalent to 25 mg of P57/kg), the peak plasma level of P57 was achieved in 0.6 h; upon intravenous administration, the plasma clearance rate of P57 was 1.09 L/h/kg; the level of P57 in plasma and tissues (brain, liver, kidney, and intestine) was determined by UPLC-MS. P57 was rapidly distributed and eliminated from the tissues within 4 hours; the level of tissue distribution was highest in the kidney, followed by liver and brain.

Gastric stability presents a significant challenge. In simulated gastric fluid, hoodigogenin A (the aglycone of P57) was stable (2% degradation in 60 minutes), whereas P57 itself was unstable (45% degradation in 30 minutes); in simulated intestinal fluid, P57 was degraded to an extent of 8% in 180 minutes, while hoodigogenin A was stable; hoodigogenin A was efficiently transported by passive diffusion across Caco-2 and MDR1-MDCK monolayers. This indicates that P57 itself undergoes partial gastric degradation, with the aglycone hoodigogenin A potentially being the bioavailable entity after oral ingestion.

The mechanism of action of P57 is debatable, as there was no detectable P57 in the brain after oral administration in CD1 female mice. P57, the glycoside thought to suppress appetite, shows low bioavailability and rapid degradation in the body. These pharmacokinetic limitations represent a major challenge to translating preclinical findings to clinical benefit.

10. Quality Control and Adulteration

The authenticity of commercial products containing oxypregnane glycosides has been an ongoing scientific concern. A developed UPLC method was successfully applied to the identification of 12 oxypregnane glycosides in four different species of Hoodia, 23 related genera, and 35 dietary supplements that claim to contain H. gordonii; UPLC profiles of various plant samples were compared for the presence of oxypregnane glycosides, and different sample matrices were successfully analyzed across a wide range of formats including gels, capsules, tablets, sprays, tea bags, snack bars, powders, and juices.

Adulteration among diet and weight management supplements occurs frequently by the use of active pharmaceuticals as adulterants to intensify the anticipated effect.

11. Safety Considerations

Hoodia gordonii

Little is known about the safety of hoodia, but the one small study in people raised concerns; in that study, participants taking hoodia had more adverse effects, including nausea, vomiting, dizziness, and odd skin sensations, than those taking placebos; the researchers also saw clinical and safety concerns related to blood pressure and heart measures.

Alarming side effects of H. gordonii products, including increased blood pressure and elevated pulse rate, have been reported. A H. gordonii-containing product tested for sympathomimetic activity via isolated organ experiments on rat uterine rings revealed smooth muscle relaxant effect with a substantial component mediated through β-adrenergic receptors. Chromatographic comparison confirmed that the herbal product contained Hoodia spp. extract, and its cardiovascular effects may be linked to the compounds of the plant.

Hoodia gordonii extracts are classified as novel foods in Great Britain and require authorisation from the Food Standards Agency (FSA) before they can be legally marketed in food supplements; the European Food Safety Authority (EFSA) assessed hoodia gordonii dried extracts as a novel food ingredient in 2010 and did not grant a safety authorisation.

Although Hoodia gordonii seems to have a desired effect on appetite and weight loss, this effect may at least in part be a secondary symptom of the serious adverse effects that are associated with consumption of the high doses required to achieve therapeutic clinical effect.

Little is known about whether it is safe to use hoodia during pregnancy or while breastfeeding.

Caralluma fimbriata

Caralluma fimbriata is considered safe for consumption; the U.S. Food and Drug Administration (FDA) added it to the GRAS (Generally Recognized as Safe) list of food ingredients in 2014. The GRAS status of the extract of C. fimbriata has opened the possibility of developing anti-obesity/appetite-suppressant products from other species of Caralluma. In controlled clinical trials, both CFE and placebo for 12 weeks caused only numerical (non-significant) reductions in anthropometric parameters. Gastrointestinal side effects have been noted but not systematically characterized across all trials.

Drug Interactions

There are no well-characterized pharmacokinetic drug interaction studies for oxypregnane glycosides in humans. Preclinical data on P57 indicate: an oxypregnane steroidal glycoside P57AS3 is reported to be the active constituent of the sap extract responsible for anorexigenic activity; no information is available about its metabolic stability, intestinal transport, and interaction with drug metabolizing enzymes in humans. Given the cardiovascular signals observed in human studies with H. gordonii, caution is warranted in combination with antihypertensive agents or cardiovascular medications. Caution is advised in patients with cardiovascular conditions or compromised hepatic function.

12. Regulatory and Conservation Status

Hoodia gordonii extracts are classified as novel foods in Great Britain and require authorisation from the Food Standards Agency (FSA); the European Food Safety Authority (EFSA) assessed hoodia gordonii dried extracts as a novel food ingredient in 2010 and did not grant a safety authorisation. Caralluma fimbriata is considered safe for consumption and the U.S. FDA added it to the GRAS list of food ingredients in 2014. Several species of the stapeliads, a group of stem succulents belonging to the family Apocynaceae, are reported on in the ethnopharmacology literature; the most important of these plants is Hoodia gordonii, which has risen from an almost forgotten spiny desert plant to an important commercial appetite-suppressant herbal.

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