Extract of succulent has dual action in moderating anxiety, study shows

By Hank Schultz

- Last updated on GMT

Extract of succulent has dual action in moderating anxiety, study shows

Related tags: Brain

A study published released recently on Zembrin, a branded extract of Sceletium tortousom, shows the product’s effects within the amygdala, the portion of the brain stem where the body’s “threat circuitry” lies.

The study, sponsored jointly by PLT Health Solutions Inc. and HG&H Pharmaceuticals Pty. Ltd. used functional magnetic resonance Imaging (FMRI) technology to study the effects of acute (short term) supplementation with Zembrin on this of the human brain. The results provide the first evidence for the areas of brain where Zembrin’s anti-anxiety activity acts, and confirmation of the potential for Zembrin to help in the management of stress.

The study is the first of it’s kind to look at the combined effect of a serotonin reuptake and PDE4 inhibitor, said Barbara Davis, PhD, PLT’s director of medical and science affairs.

“We are putting a lot of effort, money and time into evaluating Zembrin. In this type of study we understand the two activities, the PDE4 and the selective serotinin reuptake inhibition,”​ Davis told NutraIngredients-USA.

“Anxiety is characterized by hyper-responsivity to mild threats and the amygdala is the part of the brain that manages threat activity. This study is the first of its kind to directly examine the effects of these types of compounds on brain activity. It further supports the science on the mechanisms of action for Zembrin, and has pioneered the use of brain-imaging technology to evaluate and validate the activity of a plant used for centuries by the San people of southern Africa,​ she added.

Sceletium tortuosum​ is a succulent native to South Africa.  It has a centuries-long history of use by the indigenous San people in dealing with the emotional and physical stress of a leading a nomadic lifestyle in a harsh environment, Davis said.

The activiy of the signaling molecule serotonin within the brain is well understood, and inhibiting the too-rapid reuptake of this molecule has been a mechanism of action for numerous antidepressant medications on the market.  PDE4 is an enzyme that regulates the levels of cyclic AMP within the brain and is found to be elevated in depressed individuals.  Some pharmaceuticals that inhibit this cascade, Rolipram being one example, have shown to have some effectiveness in treating depression via this a novel pathway.

Study details

In the double-blind, placebo-controlled study, titled Acute effects of Sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus ​and published in the journal Neuropsychopharamcology, 16 healthy individuals were supplemented with Zembrin and then asked to perform both perceptual load and emotion masking tasks.  The individuals had a mean age of 19.2 years and were all free of diagnosed mental illness.

 In one perceptual load task, called the high load condition, participants were asked to remember whether letter strings superimposed over the image of a threatening face contained two specified letters.  In the second test, particpants had to remember whether a letter string contained only one specific letter.  The functional magnetic resonance imaging was used to show how much the amygdala “lighted up” in response to teh threats inherent in these tasks.

“In sum, we show here that the dual 5-HT reuptake and PDE4 inhibitor Zembrin reduces amygdala reactivity to unattended facial fear and also decouples amygdala–hypothalamus connectivity. These results support the potential anxiolytic actions of Zembrin and provide a foundation for exploring the clinical potential of dual PDE4 and 5-HT reuptake inhibitors for the treatment of anxiety disorders and depression,”​ the researchers concluded.

Davis said a big advantage of Zembrin is that the product shows no side effects.  It has been no the market in South Africa with hundreds of thousands of doses already having been administred with no serious adverse events to report, she said.

Patent granted

In a related development, In a related development, PLT Health Solutions announced that HG&H Pharmaceuticals has been awarded U.S. Patent #8,552,051 covering the use of one of Zembrin’s key alkaloids – mesembrenone – for its PDE4 and serotonin-reuptake inhibition properties.

“Zembrin is distinguished by its relatively low level of mesembrine and relatively high level of mesembrenone. The U.S. patent recently awarded to HG&H Pharmaceuticals protects the modulation of 5-HT and PDE4 and the application of mesembrenone as a PDE4 inhibitor,”​ said Seth Flowerman, director of business development at PLT Health Solutions.

Source: Neuropsychopharmacology
Volume 38, pages 2708-2716
Acute effects of Sceletium tortuosum (Zembrin), a dual 5-HT reuptake and PDE4 inhibitor, in the human amygdala and its connection to the hypothalamus.​”
Authors: Terberg et al

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