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International Journal of Cosmetic Science on Acetyl Hexapeptide 3

Volume 24 Issue 5 Page 303
October 2002

A synthetic hexapeptide (Argireline) with antiwrinkle activity
C. Blanes-Mira*, J. Clemente , G. Jodas , A. Gil3, G. Fernández-Ballester*, B. Ponsati , L. Gutierrez , E. Pérez-Payá and A. Ferrer-Montiel*

Botulinum neurotoxins (BoNTs) represent a revolution in cosmetic science because of their remarkable and long-lasting antiwrinkle activity. However, their high neurotoxicity seriously limits their use. Thus, there is a need to design and validate non-toxic molecules that mimic the action of BoNTs. The hexapeptide Ac-EEMQRR-NH2 (acetyl hexapeptide -3, coined Argireline) was identified as a result of a rational design programme. Noteworthy, skin topography analysis of an oil/water (O/W) emulsion containing 10% of the hexapeptide on healthy women volunteers reduced wrinkle depth up to 30% upon 30 days treatment. Analysis of the mechanism of action showed that acetyl hexapeptide-3 significantly inhibited neurotransmitter release with a potency similar to that of BoNT A, although as expected, it displayed much lower efficacy than the neurotoxin. Inhibition of neurotransmitter release was due to the interference of the A-Hex-3 peptide with the formation and/or stability of the protein complex that is required to drive Ca2+-dependent exocytosis, namely the vesicular fusion (known as SNARE) complex. Notably, this peptide did not exhibit in vivo oral toxicity nor primary irritation at high doses. Taken together, these findings demonstrate that Argireline is a non-toxic, antiwrinkle peptide that emulates the action of currently used BoNTs. Therefore, this hexapetide represents a biosafe alternative to BoNTs in cosmetics.

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