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Introduction to wrinkles and hexapeptide action on the skinOne of the most striking signs of skin aging is the relative intensity of frown and wrinkle lines of the forehead, glabella, lateral periorbital area as well as the intensity of chin, upper lip wrinkling, nasolabial folds, nasal flare and platysma neck bands among others Reference 1.
This can occur naturally over time and is identified by certain biochemical, histological and physiological changes that are enhanced by environmental exposure. There are, however, other secondary factors that can cause characteristic folds, furrows and creases of the face, such as, the constant pull of gravity, frequent and constant positional pressure of the skin of the face (e.g. during sleep) or repeated facial movements caused by the contraction of the muscles of facial expression Reference 1 & 2. Physiologically, the formation of wrinkles appears to be due, at least partly, by the excessive stimulation of the muscle fibers in the face, which pull inwards the skin-giving rise to the well-known wrinkle Reference 1& 3. Thus, a useful strategy to reduce the intensity of wrinkle lines is to down-regulate muscle action either directly or by attenuating the activity of the innervating neuron Reference 1,3 & 5. In support of this tenet, treatment with BoNT A significantly reduces the intensity of frown and wrinkle lines. BoNTs strongly inhibits the Ca 2+ -dependent neurotransmitter release in neurons Reference 6 & 7. These proteins are metalloproteases that specifically cleave synaptic proteins essential for regulated neuronal exocytosis Reference 6 & 7, specifically the vesicular protein VAMP, and the membrane proteins syntaxin and SNAP-25 Reference 7. As a result, the critical protein fusion complex assembled by these proteins, known as SNARE complex, is destabilized preventing vesicle fusion with plasma membrane, and consequently abrogating Ca 2+ -triggered exocytosis Reference 7. Although botulinum neurotoxins, specially BoNT A (BOTOX®), has been extensively used to attenuate facial aging signs, its use is limited because of its high toxicity (human LD50 2,500 biologic mouse units) Reference 1 & 6. Paradoxically, BoNT A is the most potent toxin known to mankind and, therefore, BOTOX ® treatment has to be under strict medical control Reference 1,3 & 5. To circumvent this limitation, small molecules that mimic the action of BoNTs is being pursued Reference 8-10. In this regard, synthetic peptides of greater or equal than 20-mer that emulate the amino acid sequence of the synaptic protein SNAP-25 were shown to be specific inhibitors of neurosecretion at micromolar concentrations Reference 8-10. The length of these peptides, however, along with a poor membrane permeability significantly limited their cosmetic utility. Accordingly, there is a need to identify new sequences that are shorter while preserving a biological activity. We have used rational design to address this issue. We report the identification of a 6-mer peptide (Ac-EEMQRR-NH2), patterned after the N-end of the N-terminal domain of SNAP-25 (aa 12-17), that interferes with the assembly of the SNARE ternary complex, and inhibits Ca 2+ -dependent catecholamine release from chromaffin cells. This hexapeptide was coined with the name ARGIRELINE®. Noteworthy, topical use of O/W emulsions containing 10% of this hexapeptide reduced the intensity of wrinkles in the lateral preorbital area of healthy human volunteers. Toxicological and irritation primary data indicate that the hexapeptide is well tolerated. Collectively, these findings demonstrate the feasibility of the rational strategy to find peptide-based mimetics of BoNTs action, and indicate that this hexapeptide is a biosafe cosmetic alternative to attenuate facial wrinkles. For further clinical data on Argireline®
The anti-wrinkle and anti-aging properties of this hexapeptideAt a 10% inclusion rate of this non-toxic, non-irritant hexapeptide molecule, is was noted that it modulates the excessive stimulation of the facial muscles, relaxing facial tension and reduces the depth of already formed wrinkles. This hexapeptide is the main active ingredient used in Créme de Vie, and clients consistently get great results from using it. For more on the effect that our Créme de Vie has on your skin and on wrinkles, please click here. Active ingredients used in Créme de Vie |
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