WCD: Palmitoyl Pentapeptide Improves Photo-aged Skin

By Jill Stein

Special to DG News

PARIS, FRANCE -- July 2, 2002 -Results of a randomised, double-blind trial suggest palmitoyl pentapeptide (Pal-KTTKS) improves the appearance of photodamaged facial skin.

Dr. Larry Robinson, with Procter & Gamble Company, Cincinnati, Ohio, United States, presented the findings here at the 20th World Congress of Dermatology (WCD).

Palmitoyl pentapeptide is a lipophilic modified peptide originally developed based on wound healing research and currently being investigated as an anti-aging ingredient. The peptide was developed by Sederma SA in Paris, France, and is being tested by Sederma and Procter & Gamble.

The 14-week, randomised double-blind, split-face study compared the technical and subjective efficacy of a facial skin care formulation containing 3 ppm palmitoyl pentapeptide versus a non-peptide formulation.

The trial consisted of a two-week preconditioning period and a 12-week treatment period. Each formulation was tested on 92 women aged 35 to 55 years. Subjects were generally healthy and had moderate to severe photodamaged facial skin and Fitzgerald skin types of I, II, or III. During the 12-week treatment period, subjects were given both test formulations and instructed to use them twice a day, in the morning and night, on the right or left side of their face.

Facial lines and texture were assessed by image analysis and trained visual grading of high-resolution digital images taken at baseline and at weeks 4, 8, and 12. In addition, subjects completed a self-assessment questionnaire regarding their own skin appearance at weeks 4, 8, and 12.

Results showed that the addition of 3 ppm palmitoyl pentapeptide significantly decreased facial lines and wrinkles as measured by image analysis at weeks 4, 8, and 12 relative to placebo. Trained visual grading of images also demonstrated a significant reduction in the appearance of fine lines/wrinkles at weeks 8 and 12.

Self-assessment data indicated that the peptide formulation showed improvements in the appearance of age spots, dark circles under the eyes, and skin firmness.

Overall, the results suggest that palmitoyl pentapeptide improves the appearance of photo-aged skin both by standardized measures and self-assessment, Dr. Robinson said.

The study was sponsored by Procter & Gamble

International Journal of Cosmetic Science
Volume 24 Issue 5 Page 303 - October 2002
doi:10.1046/j.1467-2494.2002.00153.x

A synthetic hexapeptide (Argireline) with antiwrinkle activity

C. Blanes-Mira, J. Clemente, G. Jodas, A. Gil, G. Fernandez-Ballester, B. Ponsati, L. Gutierrez, E. Perez-Paya and A. Ferrer-Montiel

Synopsis

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 (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 Argireline 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 hexapeptide 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.

 

Journal of Neurochemistry
Volume 88 Issue 1 Page 124 - January 2004
doi:10.1046/j.1471-4159.2003.02133.x

Small peptides patterned after the N-terminus domain of SNAP25 inhibit SNARE complex assembly and regulated exocytosis

Clara Blanes-Mira, Jaime M. Merino, Elvira Valera, Gregorio Fernandez-Ballester, Luis M. Gutierrez, Salvador Viniegra, Enrique Perez-Paya and Antonio Ferrer-Montiel

Abstract

Synthetic peptides patterned after the C-terminus of synaptosomal associated protein of 25 kDa (SNAP25) efficiently abrogate regulated exocytosis. In contrast, the use of SNAP25 N-terminal-derived peptides to modulate SNAP receptors (SNARE) complex assembly and neurosecretion has not been explored. Here, we show that the N-terminus of SNAP25, specially the segment that encompasses 22Ala-44Ile, is essential for the formation of the SNARE complex. Peptides patterned after this protein domain are potent inhibitors of SNARE complex formation. The inhibitory activity correlated with their propensity to adopt an -helical secondary structure. These peptides abrogated SNARE complex formation only when added previous to the onset of aggregate assembly. Analysis of the mechanism of action revealed that these peptides disrupted the binary complex formed by SNAP25 and syntaxin. The identified peptides inhibited Ca²⁺ - dependent exocytosis from detergent-permeabilized excitable cells. Noteworthy, these amino acid sequences markedly protected intact hippocampal neurones against hypoglycaemia-induced, glutamate-mediated excitotoxicity with a potency that rivaled that displayed by botulinum neurotoxins. Our findings indicate that peptides patterned after the N-terminus of SNAP25 are potent inhibitors of SNARE complex formation and neuronal exocytosis. Because of their activity in intact neurones, these cell permeable peptides may be hits for antispasmodic and analgesic drug development.

Before VISIFIRM™
(transmission occurs)

After VISIFIRM™
(no transmission)

Aging and sun exposure reduces collagen, causing wrinkles.

VISIFIRM™ restores collagen and plumps up skin, reducing wrinkles.