Acetyl Hexapeptide-3 is a synthetic peptide commonly researched for its potential action in dermal wrinkling. Researchers developed Acetyl Hexapeptide-3 as a competitive SNAP25 inhibitor. SNAP-25 is a component of the SNARE complex, which is central to synaptic vesicle Ca(2+)-dependent exocytosis. By inhibiting exocytosis, Acetyl Hexapeptide-3 may potentially block the release of acetylcholine, a neurotransmitter involved in muscle contractions.
Acetyl Hexapeptide-3 is considered a milder and less invasive alternative to bacterial toxins. Acetyl Hexapeptide-3 may have the potential to act directly through the skin.(2) The peptide may also help in the management of blepharospasm or scarring. Animal studies also suggest the peptide’s potential impact on collagen synthesis. Furthermore, palmitoylated peptide versions may even help block pain nociception in individuals suffering from chronic aches.
Molecular formula: C34H60N14O12S
Molecular weight: 889.0 g/mol
Other known titles:
- Acetyl Hexapeptide-8
Research and Clinical Studies
Acetyl Hexapeptide-3 and Wrinkles
Botulinum neurotoxins (BoNTs) may possibly reduce wrinkles, but their apparent neurotoxicity limits their use. To overcome this, Acetyl Hexapeptide-3 was designed to mimic the action of BoNTs and possibly bypass toxicity. One study reports that an emulsion containing Hexapeptide was suggested to reduce wrinkle depth by up to 30% after 30 days in 10 test subjects.(2)
An additional trial investigated the impact of Acetyl Hexapeptide-3 on the skin properties of 24 subjects and reported similar results.(3) Subjects were randomly assigned to receive the peptide or placebo for 60 days. Skin microtopography and transepidermal water loss (TEWL) were measured at different times. The results suggested that Acetyl Hexapeptide-3 had possible anti-wrinkle activity and might decrease TEWL.
The potential of the peptide does not appear to depend on the type of skin. For example, another clinical study involved 52 female subjects and was conducted over 29 days to evaluate the impact of Acetyl Hexapeptide-3 for wrinkle improvement.(4) After the trial, the scientists observed statistically improved wrinkles and skin hydration in all groups.
In another clinical trial, the scientists report that compared to the placebo, “the total anti-wrinkle efficiency in the treatment group was 48.9%, the depth of the wrinkles was notably reduced.“(5)
Animal studies suggest that Acetyl Hexapeptide-3 may help improve wrinkles and fine lines by interacting with collagen synthesis, although this mechanism is poorly studied. For example, one trial in aged mice who were given the peptide for six weeks exhibited an apparent improvement in the histological structure of the skin tissue, with an apparent increase in type I collagen fibers and a decrease in type III collagen fibers.(6) The study concluded that Acetyl Hexapeptide-3 might rejuvenate aging skin through the histological structure of the skin tissue.
Acetyl Hexapeptide-3 and Blepharospasm
Blepharospasm is characterized by involuntary contractions of the eyelid muscles that can impair vision and daily activities. One study investigated the potential of Acetyl Hexapeptide-3 for blepharospasm in a clinical setting.(7) The trial involved 24 subjects with blepharospasm who received the peptide in a double-blind, placebo-controlled, randomized design. The primary outcome measured was the time to return to baseline Jankovic Blepharospasm Rating Scale (JBRS) after subjects received neurotoxic protein control and the peptide provided to subjects monthly. Only subjects with a regular response pattern to 3-monthly neurotoxins were included in the study. There was a trend for a longer period until the return to baseline JBRS in the active group compared to the placebo group, with an average of 3.7 months versus 3.0 months. Additionally, subjects in the active group tended to have better scores than those in the placebo group. Interestingly, the researchers also report that “One-third (4/12) of the patients in the active group had a considerable extension of symptom control after [neurotoxins] (range: 3.3-7.1 months).”
Acetyl Hexapeptide-3 and Scarring
According to one retrospective clinical study of 26 subjects with skin disorders, Acetyl Hexapeptide-3 may also support the mitigation of surgical scars or unappealing skin tags.(8) The scientists measured skin quality parameters, took photographs, and performed an investigator’s clinical assessment before and after the study. Researchers suggested that Acetyl Hexapeptide-3 is a potentially “effective alternative to the invasive procedures, to improve the quality of life in patients with some skin disorders such as cancer, surgical scars, hidradenitis, aging wrinkles.“(8)
Acetyl Hexapeptide-3 and Chronic Pain
The palmitoylated version of Acetyl Hexapeptide-3, DD04107, has been studied for its potential analgesic activity in chronic inflammatory and neuropathic pain models.(9) It was suggested to be impactful in blocking the inflammatory recruitment of ion channels and the release of calcitonin gene-related peptides, resulting in anti-hyperalgesia and anti-allodynia.
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- 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.
- 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
- Raikou, V., Varvaresou, A., Panderi, I., & Papageorgiou, E. (2017). The efficacy study of the combination of tripeptide-10-citrulline and acetyl hexapeptide-3. A prospective, randomized controlled study. Journal of cosmetic dermatology, 16(2), 271–278. https://doi.org/10.1111/jocd.12314
- 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. https://doi.org/10.5021/ad.2019.31.3.263
- 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. https://doi.org/10.3109/14764172.2012.759234
- 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. https://doi.org/10.3109/14764172.2013.769273
- Lungu, C., Considine, E., Zahir, S., Ponsati, B., Arrastia, S., & Hallett, M. (2013). Pilot study of topical acetyl hexapeptide-8 in the treatment for blepharospasm in patients receiving botulinum toxin therapy. European journal of neurology, 20(3), 515–518. https://doi.org/10.1111/ene.12009
- Palmieri, B., Noviello, A., Corazzari, V., Garelli, A., & Vadala, M. (2020). Skin scars and wrinkles temporary camouflage in dermatology and oncoesthetics: focus on acetyl hexapeptide-8. La Clinica terapeutica, 171(6), e539–e548. https://doi.org/10.7417/CT.2020.2270
- Ponsati, B., Carreño, C., Curto-Reyes, V., Valenzuela, B., Duart, M. J., Van den Nest, W., Cauli, O., Beltran, B., Fernandez, J., Borsini, F., Caprioli, A., Di Serio, S., Veretchy, M., Baamonde, A., Menendez, L., Barros, F., de la Pena, P., Borges, R., Felipo, V., Planells-Cases, R., … Ferrer-Montiel, A. (2012). An inhibitor of neuronal exocytosis (DD04107) displays long-lasting in vivo activity against chronic inflammatory and neuropathic pain. The Journal of pharmacology and experimental therapeutics, 341(3), 634–645. https://doi.org/10.1124/jpet.111.190678
Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.