Caralluma Fimbriata Cuts Appetite in PWS via Brain Receptors

observational-study PMID: 30353709

Caralluma Fimbriata Cuts Appetite in PWS via Brain Receptors

Quick Summary: Researchers tested Caralluma fimbriata extract on mice modeling Prader-Willi syndrome (PWS), a condition causing constant hunger. The extract reduced eating by acting on 5-HT2c brain receptors, which help control fullness signals. This points to a potential way to manage overeating in PWS, but more human studies are needed.

What the Research Found

Scientists explored how Caralluma fimbriata extract (CFE), a plant-based supplement, affects hunger in a mouse version of Prader-Willi syndrome (PWS). PWS is a genetic disorder linked to uncontrollable eating due to issues in a specific gene region on chromosome 15. In these mice, CFE strongly lowered food intake, especially at higher doses.

Key discoveries include:
- CFE works through 5-HT2c receptors in the brain—these are like switches that signal "I'm full" to stop eating.
- Blocking these receptors with a drug (SB242084) canceled out CFE's hunger-reducing effects, proving the receptor's role.
- In PWS mice, other appetite triggers (like 2DG, a sugar blocker, and MA, a hormone mimic) oddly reduced eating even more than in normal mice, showing messed-up hunger signals in PWS.
- Brain scans confirmed less activity in hunger-control areas after CFE treatment, matching the reduced eating behavior.

These findings explain why CFE might help curb the endless appetite seen in PWS.

Study Details

Who was studied: Male mice with a Snord116 gene deletion (mimicking PWS) and normal "wild-type" mice for comparison. These mice represent the hyperphagia, or extreme hunger, in human PWS.
How long: 9 weeks of daily CFE treatment, followed by short 30-minute tests to measure eating right after appetite triggers.
What they took: Oral CFE mixed into food at low (33 mg/kg body weight) or high (100 mg/kg) doses. The high dose worked best. Tests used injections of SB242084 (to block 5-HT2c receptors), 2DG (to mimic low blood sugar), or MA (to activate fullness hormones).

Food intake dropped significantly in treated PWS mice (p < 0.001), with the high-dose group showing the strongest results. Brain activity markers (like c-Fos) backed this up.

What This Means For You

If you or a loved one has Prader-Willi syndrome, this research suggests Caralluma fimbriata could be a natural option to ease constant hunger by targeting brain fullness signals. It's not a cure, but it might help manage overeating, which affects daily life and health in PWS.

For general weight management, CFE shows promise as an appetite suppressant via serotonin receptors (5-HT2c acts like a natural "stop eating" button). However, it's based on mice—talk to a doctor before trying supplements, especially for kids or those with genetic conditions. This could inspire new PWS treatments focused on brain pathways.

Study Limitations

This was an animal study, so results might not fully apply to humans—PWS in people involves more complex genetics and behaviors. Sample sizes weren't detailed, which could affect reliability. The eating tests were short-term (just 30 minutes), so we don't know about long-term effects or safety. It also didn't explore how CFE affects other body systems or why certain hunger triggers acted differently in PWS mice. More human trials are essential before recommending it widely.

Source: PubMed (2018) observational study on Snord116del mice.

Key Findings

The study demonstrated that Caralluma fimbriata extract (CFE) significantly decreased food intake in Snord116del mice, a model for Prader-Willi syndrome (PWS). Co-administration of the 5-HT2c receptor antagonist SB242084 reversed this appetite-suppressing effect, confirming the receptor’s role in CFE’s mechanism. Additionally, 2DG (glucose analog) and MA (melanocortin agonist) induced lower food intake in Snord116del mice compared to wild-type (WT) controls (p < 0.001), suggesting disrupted satiety signaling in the PWS model. Immunohistochemical analysis of hypothalamic neural activity aligned with behavioral outcomes, reinforcing the neurobiological basis of CFE’s effects.

Study Design

This was an observational study using male Snord116del mice (n = unspecified) and WT littermates. Mice underwent chronic CFE treatment (33 mg/kg or 100 mg/kg) for 9 weeks, followed by acute appetite-stimulating tests with SB242084 (5-HT2c antagonist), 2DG (glucoprivic agent), or MA (melanocortin agonist). Food intake was measured over 30 minutes post-treatment. Hypothalamic neural activity was assessed via c-Fos immunohistochemistry.

Dosage & Administration

CFE was administered orally at 33 mg/kg or 100 mg/kg, mixed into standard chow. The 100 mg/kg dose (SNO100CFE) showed stronger appetite suppression. SB242084 was delivered intraperitoneally (IP) 30 minutes before food access. 2DG and MA were also administered IP.

Results & Efficacy

Chronic CFE treatment reduced food intake in Snord116del mice, with SNO100CFE showing the most pronounced effect (p < 0.001).
SB242084 co-administration reversed CFE-induced suppression, increasing food intake by ~40% compared to CFE alone (p < 0.001).
2DG and MA paradoxically reduced food intake in Snord116del mice vs. WT controls (p < 0.001), indicating altered metabolic and melanocortin signaling.
Hypothalamic c-Fos expression (a neural activation marker) correlated with reduced feeding behavior in CFE-treated mice but was attenuated by SB242084.

Limitations

Observational design: Cannot establish causality, only associations.
Unspecified sample size: Limits reproducibility and statistical power assessment.
Mouse model constraints: Snord116del mice may not fully replicate human PWS pathophysiology.
Short acute testing: 30-minute food intake measurements may not reflect long-term efficacy or safety.
Mechanistic gaps: While 5-HT2cR involvement was confirmed, downstream pathways remain unclear.

Clinical Relevance

This study suggests CFE may target 5-HT2c receptors to suppress appetite in PWS, offering a potential therapeutic avenue. However, results are limited to a preclinical mouse model, and human trials are needed to validate efficacy and safety. For supplement users, CFE’s appetite-reducing effects might be relevant for hyperphagia management, but current evidence does not support clinical application without further research. The findings highlight the importance of neuroreceptor-specific mechanisms in PWS-related feeding disorders, guiding future drug development.

Source: PubMed (2018) | Type: Observational study | Duration: 9 weeks chronic treatment + acute testing.