Synthetic peptide Acetyl Hexapeptide-3 (Argireline) is studied in the lab. N-acetyl-L-alpha-glutamyl-L-alpha-glutamyl-L-methionyl-L-glutaminyl-L-arginyl-L-arginine amide is a chain of six amino acids linked in a particular sequence. Recent research has focused on how Acetyl hexapeptide-3 (Ach-3) may influence neurotransmitter release at neuromuscular synapses.

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The SNARE (soluble NSF attachment protein receptor) includes a component called SNAP25 (synaptosome-associated protein 25), and it is theorized that Acetyl Hexapeptide-3 may act as a competitive inhibitor of this protein. The 25-kDa molecular weight of this protein inspired its name. Ca(2+)-dependent exocytosis of synaptic vesicles, in which neurotransmitters like acetylcholine are released, is thought to be facilitated by the SNARE complex. Muscle contractions are associated with the neurotransmitter acetylcholine.

Studies suggest that Acetyl Hexapeptide-3 may impede muscle contraction by interfering with the function of neuromuscular synapses, potentially by blocking acetylcholine exocytosis. This method looks comparable to how bacterial toxins, such as the toxin generated by Clostridium botulinum - (BoNTs) - are hypothesized to interact and block neuromuscular synapses. However, research suggests that Acetyl Hexapeptide-3, with its acetyl moiety attached to the N-terminus, may have an advantage in diffusion through the epidermis.

Investigations purport that Acetyl Hexapeptide-3 may also reduce nociception and interact with other nervous system function elements. The peptide might influence collagen synthesis and breakdown as well.

Acetyl Hexapeptide-3 and Dermal Topography

Acetyl hexapeptide-3 has suggested promise in experimental studies, with results suggesting it may reduce wrinkle depth by as much as 48.9% and smooth out the skin surface by 30%. The researchers speculate the peptide works by blocking the release of acetylcholine and other neurotransmitters at the neuromuscular synapses. They also agree that the hexapeptide's "inhibition of neurotransmitter secretion was due to the interference of the hexapeptide with the formation and strength of the protein complex that is needed to drive Ca(2+)-dependent exocytosis, i.e., the vesicular fusion (known as SNARE) complex."

As suggested by the research above, Acetyl hexapeptide-3 has been hypothesized to work primarily via competitive suppression of synaptosomal-associated protein-25 (SNAP-25). It may act similarly to bovine neurotoxin type 1 (BoNTs), blocking the development of the ternary soluble N-ethylmaleimide sensible factor attachment protein receptor (SNARE) complex, preventing neurotransmitter release. Acetyl hexapeptide-3 has been postulated to work by blocking the contraction of intrinsic muscles.

Acetyl Hexapeptide-3 and Collagen Synthesis

Collagen production has been studied about Acetyl Hexapeptide-3 because this extracellular matrix protein is thought to be important for the structure and elasticity of connective tissues. Histological studies of cutaneous tissue have suggested that this peptide may affect collagen synthesis.

Extensive 6-week studies in mice purport the peptide may enhance type I collagen fibers while decreasing type III collagen fibers. The scientists utilized hematoxylin-eosin (HE) and picrosirius-polarization (PSP) stains to analyze these histological alterations in the dermal tissues. Also, using Image-ProPlus, they examined the relative amounts of type I and type III collagen fibers in a semi-quantitative manner.

Findings implied that Acetyl Hexapeptide-3 may lessen scarring during and after tissue regeneration by decreasing type III collagen fibers. The elasticity of scarred tissue is hypothesized to improve "from 33,5% to 40,5% (...) in lateral-medial zone of the neck and malar area; from 24% to 31,5% (...) in right lateral-medial area of the neck and malar area; and from 25,5% to 38% (...) in forehead and chin area" after presentation of the peptide, as suggested by the findings of some researchers.

Acetyl Hexapeptide-3 and Nociception

Several in vitro models have been used to investigate the possible impacts of Acetyl Hexapeptide-3 on a wide range of cellular and molecular systems. The possible effects on ion channels and inflammatory processes in nociceptive disorder and hyperalgesia must be investigated.

Acetyl Hexapeptide-3 (DD04107) is a palmitoylated form of Acetyl Hexapeptide-3 that has been studied for its ability to alleviate nociceptive stimuli in animal models of chronic inflammatory and neuropathic hyperalgesia. In particular, the palmitoylated Acetyl Hexapeptide-3 may block the release of neuromodulators involved in nociceptive signaling, as the study's authors suggested. It seems to do this via blocking Ca(2+)-dependent exocytosis of certain neuromodulators by interacting with SNAP-25. Therefore, the palmitoylated form of Acetyl Hexapeptide-3 may have anti-hyperalgesia and anti-allodynic potential by inhibiting the inflammatory recruitment of TRPV1 channels.

TRPV1 channels are ion channels located largely on sensory nerve fibers, particularly those implicated in pain perception. Activation of these channels is thought to result in the production and transmission of pain signals in response to various stimuli, including heat, inflammatory mediators, and chemical irritants.

Carrageenan-induced inflammation is used in research to create models of acute inflammatory pain, and it has been hypothesized that the palmitoylated version of Acetyl Hexapeptide-3 may have anti-inflammatory activity by decreasing paw volume (a measure of inflammation) and dampening mechanical hypersensitivity.

Researchers interested in further studying this peptide can navigate the corepeptides.com website for more high-quality research compounds.

 

References

[i] Grosicki, M., Latacz, G., Szopa, A., Cukier, A., & Kieć-Kononowicz, K. (2014). The study of cellular cytotoxicity of argireline – an anti-aging peptide. Acta biochimica Polonica, 61(1), 29–32.

[ii] Blanes-Mira, C., Clemente, J., Jodas, G., Gil, A., Fernández-Ballester, G., Ponsati, B., Gutierrez, L., Pérez-Payá, E., & Ferrer-Montiel, A. (2002). A synthetic hexapeptide (Argireline) with antiwrinkle activity. International journal of cosmetic science, 24(5), 303–310. https://doi.org/10.1046/j.1467-2494.2002.00153.x

[iii] Wang, Y., Wang, M., Xiao, X. S., Pan, P., Li, P., & Huo, J. (2013). The anti wrinkle efficacy of synthetic hexapeptide (Argireline) in Chinese Subjects. Journal of cosmetic and laser therapy : official publication of the European Society for Laser Dermatology, Advance online publication.

[iv] An, J. H., Lee, H. J., Yoon, M. S., & Kim, D. H. (2019). Anti-Wrinkle Efficacy of Cross-Linked Hyaluronic Acid-Based Microneedle Patch with Acetyl Hexapeptide-8 and Epidermal Growth Factor on Korean Skin. Annals of dermatology, 31(3), 263–271.

[v] Wang, Y., Wang, M., Xiao, X. S., Huo, J., & Zhang, W. D. (2013). The anti-wrinkle efficacy of Argireline. Journal of cosmetic and laser therapy : official publication of the European Society for Laser Dermatology, 15(4), 237–241.

 

 

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