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Skin Deep is a blog for dermatologists and skin care professionals with focus on theoretical, cosmetic and aesthetic dermatology. This blog is associated with ‘Dermatologists Sans Borders’ one of the largest curated groups of skin care professionals on facebook. If you are looking for non-technical information, please visit

The Embrace That SNAPS the SNARE - Argireline Part 2

Please read Argireline Part 1 and the full series here.

Acetyl hexapeptide-3 has one major advantage. BoNT/A causes permanent destruction of SNAP-25 of the SNARE complex, triggering neuronal sprout formation and a steady recovery. Acetyl hexapeptide-3 acts like a competitive inhibitor of SNAP-25, so this recovery mechanism is not triggered. It is also claimed to have an independent effect on fibroblast contraction that augments collagen synthesis. But there are many prominent disadvantages as well.

Detailed view of a neuromuscular junction: 1. ...
Detailed view of a neuromuscular junction: 1. Presynaptic terminal 2. Sarcolemma 3. Synaptic vesicle 4. Nicotinic acetylcholine receptor 5. Mitochondrion (Photo credit: Wikipedia)
In my previous post on 3 villains, I mentioned about stability, penetration and degradation of peptide molecules. This article claims that Acetyl hexapeptide-3 is good enough to combat this villians.[1] But there are two other mysterious villains in this story. Before I expose them, some shameless self promotion again.

In my article [2] (self archived preprint here) I discussed the importance of the binding of BONT/A to the SV2 receptor that facilitates its neuronal penetration. This binding is mediated by a domain of BONT/A different from its active site. Acetyl hexapeptide-3 does not have this domain. So how does it reach the inside of the neuron? (Read this on Rational Peptide Design)

BONT/A injectors would agree that, a muscle relaxant could be cosmetically enhancing if administered in the right places. A non-localised effect is unlikely to be beneficial. Does it cause sagging?

Acetyl hexapeptide-3 (like most peptides) did not have any experimental proof of efficacy. Now it has! This study[3] shows that it can increase type I collagen (but paradoxically reduces type III, problem!!). Why did they study the effect on collagen synthesis when it is sold as a muscle relaxant?

And finally, an RCT on Acetyl hexapeptide-3 that shows promising results![4] But wait, Did you see the conclusion.
“In the objective evaluation, the parameters of roughness were all decreased in the argireline group (p < 0.01), while no decrease was obvious in the placebo group (p > 0.05).” 
Separate P values for intervention arm and placebo arm. I don't have access to full article, but this means only one thing to me. They were scared (or want to hide) the actual intervention-placebo comparison. What do you think?

Embiodea (Photo credit: beapen)
The bottom line: Acetyl hexapeptide-3 is unlikely to have remarkable muscle relaxant effect, but could have a non-specific pro collagen effect with a mechanism of action different from other collagen fragments, I discussed before. A mixture of both (Argireline and Matrixyl) may give additive effect.

1. Ruiz, MA et al. "Preparation and stability of cosmetic formulations with an anti-aging peptide." Journal of cosmetic science 58.2 (2007): 157.

2. Eapen, Bell Raj. "Molecular biology of botulinum neurotoxin serotype A: a cosmetic perspective." Journal of cosmetic dermatology 7.3 (2008): 221-225.

3. Wang, Yuan et al. "The anti-wrinkle efficacy of Argireline." Journal of Cosmetic and Laser Therapy 0 (2013): 1-5.

4. Wang, Yuan et al. "The Anti-Wrinkle Efficacy of Argireline, a Synthetic Hexapeptide, in Chinese Subjects." American journal of clinical dermatology (2013): 1-7.

That concludes my discussion on skin renewal peptides. How do you rate the potential of the discussed beauty peptides?

Please read Argireline Part 1 and the full series.

Disclaimer: Matrixyl and Argireline are registered trademarks. All information presented here is given in good faith but without warranty or guarantee of any kind whatsoever, whether implied or expressed.
Read the full series here.

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About Me

As a Dermatologist and Informatician my research mainly involves application of bioinformatics techniques and tools in dermatological conditions. However my research interests are varied and I have publications in areas ranging from artificial intelligence, sequence analysis, systems biology, ontology development, microarray analysis, immunology, computational biology and clinical dermatology. I am also interested in eHealth, Health Informatics and Health Policy.


Bell Raj Eapen
Hamilton, ON