Article

The anti-wrinkle efficacy of Argireline

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Abstract

Background: Argireline, a synthetic peptide, which is patterned from the N-terminal end of the protein SNAP-25, can both reduce the degree of existing facial wrinkles and demonstrate effectively against their development. In our past studies, we found out that Argireline had a significant anti-wrinkle effect in Chinese subjects and that it was safe and well tolerated. Objective: To observe the effect of Argireline on histological changes in the skin in the aged mice induced by D-galactose. Methods: Argireline was applied to the aged mice twice daily for 6 weeks. The histological changes in skin tissue were evaluated using hematoxylin-eosin (HE) and picrosirius-polarization (PSP) stains. The amount of type I and of type III collagen fibers were also semi-quantitatively compared using software Image-ProPlus. Results: There was an improvement in the histological structure of skin tissue in the aged mice; the amount of type I collagen fibers increased (P < 0.01), while that of type III collagen fibers decreased (P < 0.05). Conclusions: This study revealed that Argireline could improve the histological structure of skin tissue and rejuvenate the aging skin.

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... We identified 21 publications where D-galactose-induced skin aging in rodents was studied [66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][82][83][84][85][86] (Table 1). ...
... These studies showed that significant changes in skin morphology occurred in rodents as a result of D-gal treatment. In particular, the data showed that the administration of D-gal in mice and rats caused skin thinning and worsening of fur quality [67,68,70,71,74,[76][77][78][79][82][83][84][85]. Also, hair color changes and unique skin appearance with wrinkles and furrows were detected [80,84] as well as the destruction of hair follicles in the skin [69,84]. ...
... In majority of the abovementioned studies, special attention was given to the quality of collagen fibers and collagen content [66-75, 78-80, 84, 86]. It was established that Dgal treatment reduced the total skin collagen in both mice and rats [66-75, 77-80, 84]: the type I collagen expression was downregulated [68,79], while the number of type III collagen fibers was increased [68]. The data presented in these studies indicate that significant collagen fiber shortening and disordering occur in D-gal-treated animals [68]. ...
Article
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Skin aging has been associated with a higher dietary intake of carbohydrates, particularly glucose and galactose. In fact, the carbohydrates are capable of damaging the skin’s vital components through nonenzymatic glycation, the covalent attachment of sugar to a protein, and subsequent production of advanced glycation end products (AGEs). This review is focused on the role of D-galactose in the development of skin aging and its relation to oxidative stress. The interest in this problem was dictated by recent findings that used in vitro and in vivo models. The review highlights the recent advances in the underlying molecular mechanisms of D-galactose-mediated cell senescence and cytotoxicity. We have also proposed the possible impact of galactosemia on skin aging and its clinical relevance. The understanding of molecular mechanisms of skin aging mediated by D-galactose can help dermatologists optimize methods for prevention and treatment of skin senescence and aging-related skin diseases.
... Then, once these ions enter the presynaptic terminal, the release of acetylcholine from the vesicles occurs [301,393]. SNAP-25 (synaptosomalassociated protein 25)-a membrane receptor protein associated with vesicles, involving the SNARE (soluble N-ethylmaleimide-sensitive factor activating protein receptor) complex-modulates this process, regulating the binding and fusion of the vesicles [301,395,396]. In detail, to form the SNARE complex, Munc-18 (mammalian uncoordinate-18) proteins must bind to syntaxin, followed by SNAP-25 and VAMP (vesicle-associated membrane protein, necessary for the synaptic vesicle's docking and fusion to the presynaptic membrane for the acetylcholine release) [397,398]. ...
... It was scientifically demonstrated that Argireline ® is a safe, effective anti-wrinkle ingredient [337,352,427], particularly suitable for eye care product formulation [345,354]. The results derived from clinical tests showed a wrinkle depth reduction of up to 16.9% within 15 days, and up to 27% within 30 days [395,396]. For performing these tests, a cream containing 10% Argireline ® was applied twice daily around the eyes by women aged 44. ...
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The “modern” cosmetology industry is focusing on research devoted to discovering novel neurocosmetic functional ingredients that could improve the interactions between the skin and the nervous system. Many cosmetic companies have started to formulate neurocosmetic products that exhibit their activity on the cutaneous nervous system by affecting the skin’s neuromediators through different mechanisms of action. This review aims to clarify the definition of neurocosmetics, and to describe the features of some functional ingredients and products available on the market, with a look at the regulatory aspect. The attention is devoted to neurocosmetic ingredients for combating skin stress, explaining the stress pathways, which are also correlated with skin aging. “Neuro-relaxing” anti-aging ingredients derived from plant extracts and neurocosmetic strategies to combat inflammatory responses related to skin stress are presented. Afterwards, the molecular basis of sensitive skin and the suitable neurocosmetic ingredients to improve this problem are discussed. With the aim of presenting the major application of Botox-like ingredients as the first neurocosmetics on the market, skin aging is also introduced, and its theory is presented. To confirm the efficacy of the cosmetic products on the market, the concept of cosmetic claims is discussed.
... 26 Another study showed that Argireline can improve the histological structure of the skin tissue in aged mice and rejuvenate aging skin. 27 Moreover, the regular use of anti-wrinkle creams containing hyaluronic acid for over 3 months shows clear and positive effects on wrinkle-depth and skin-tightness. 28 PCA results indicated that the young group and the presenile group could not be separated, suggesting that existing skin phenotypes are insufficient to describe the characteristics of these two groups. ...
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Purpose: As the human body's largest organ exposed to the external environment, the skin suffers from internal and external aging factors, leading to wrinkles, loss of elasticity, sagging, and rough appearance. However, little is known of the characteristics of skin aging of different body parts in Chinese women. Here, we study the signs of extrinsic skin aging in different body parts to identify the knowledge map of manifestations of aging in Chinese women. Patients and methods: Wrinkle and texture phenotypes and collagen samples from the face, neck, hands, and arms of 326 Chinese women were collected. The correlations between phenotypes and ages and the differences in phenotypes by age were evaluated. Results: The wrinkle and texture phenotypes around the eyes and mouth and of the hands were strongly correlated with age. Ages 32 and 58 showed the largest number of differentially changed aging phenotypes. The number of aging phenotypes increased sharply between the ages of 24 and 30, suggesting that the skin was undergoing rapid aging. Eye aging was the most rapidly changing phenotype between 19 and 30 years old. Wrinkles at the corner of the eyes showed a significant difference in the older group, suggesting an early onset and long-term effects. Conclusion: This is the first study to be performed on the characteristics of skin aging among Chinese women that takes account of multiple areas of the body. It was found that 24 years old was the time point at which the skin begins to age in Chinese women. This provides important clues for aging-related research and personalized skin care.
... It competitive inhibits the SNAP25 component of the said vesicle docking and fusion protein complex (SNARE) [6] which triggers the calcium-dependent neurotransmitter release into the synapse, a process necessary for muscle contraction [7][8][9][10]. Acetyl hexapeptide-8 is marketed as Argireline ® [11], and it has been efficiently used in cosmetics for smoothening the under-eye wrinkles and the forehead furrows [12][13][14]. After topical application at specific areas of the face, it inhibits the reactions that cause muscles to move or contract for example when forming facial expressions such as smiling or frowning [15,16]. ...
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Bioactive peptides are gaining more and more popularity in the research and development of cosmetic products with anti-aging effect. Acetyl hexapeptide-8 is a hydrophilic peptide incorporated in cosmetics to reduce the under-eye wrinkles and the forehead furrows. Hydrophilic interaction liquid chromatography (HILIC) is the separation technique of choice for analyzing peptides. In this work, a rapid HILIC method coupled to photodiode array detection operated at 214 nm was developed, validated and used to determine acetyl-hexapeptide-8 in cosmetics. Chromatography was performed on a Xbridge® HILIC BEH analytical column using as mobile phase a 40 mM ammonium formate water solution (pH 6.5)-acetonitrile mixture 30:70, v/v at flow rate 0.25 mL min−1. The assay was linear over the concentration range 20 to 30 μg mL−1 for the cosmetic formulations and 0.004 to 0.007% (w/w) for the cosmetic cream. The limits of quantitation for acetyl hexapeptide-8 were 1.5 μg mL−1 and 0.002% (w/w) for the assay of cosmetic formulations and cosmetic creams, respectively. The method was applied to the analysis of cosmetic formulations and anti-wrinkle cosmetic creams.
... Previous studies have demonstrated that type I collagen content in normal skin indicates stages of collagen remodeling [31,32]. In this study, we demonstrated that treated groups showed increased amounts of type I collagen and decreased amounts of type III collagen. ...
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Radiofrequency (RF) treatment appears to be involved in production of new collagen fibrils and the improvement of existing collagen structures; however, the molecular bases of the effect of non-invasive RF on the skin tissue have not been fully elucidated. This study reports the effects of RF associated or not with hydrolyzed collagen (HC) in the skin tissue. Wistar rats were randomly divided into four groups, according to the treatment received: control group (G1, n = 5), no treatment; subjects in group G2 (n = 5) were treated with HC; and capacitive RF was applied to the back of each subject in G3 (n = 5) and RF associated with HC in G4 (n = 5). Biopsies were taken 30 days after treatment and then were histologically processed and studied for inflammatory cell counting, collagen content, and morphometry. In addition, FGF2, CD105, and COX-2 expression was assessed by immunohistochemical staining. The most relevant changes were the increase in cellularity and accumulation of intercellular substance in RF-treated animals (G3 and G4). The greatest dermis thickness rate was observed in G4, followed by G3 and G2 (p < 0.05). RF-treated skins (G3 and G4) exhibited a significant overexpression of FGF2 (p < 0.0001) and increased microvessel density (p < 0.0001) in comparison with G1 and G2. Moreover, the amount of COX-2 was significantly higher (p < 0.0001) in dermis of RF-treated areas compared to G1 and G2, and demonstrated differences in G3 (RF) compared to G4 (RF + HC) (p < 0.0001). Our results suggests that RF treatment associated or not with HC induces FGF2 overexpression, promotes neoangiogenesis and modulates the COX-2 expression, subsequently promotes neocollagenesis, and increased thickness rate of dermis.
... Acetyl hexapeptide-3 has been reported to penetrate through the skin in vitro 3 and to contribute in collagen synthesis of type I in vivo. 4 Acetyl hexapeptide-3 is an effective anti-aging compound as already mentioned by Blanes-Mira et al. 3 The author, using silicon replicas, observed attenuation of the depth of the wrinkles after 30 days of application, when compared to vehicle. ...
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One of the most common etiologic forces for the persistence of facial rhytides is the repetitive contraction of the intrinsic muscles that are necessary for facial expression. These include the forehead lines, crow's feet, glabellar rhytides, and wrinkles in the lower face. Although filling agents such as collagen and laser procedures can help reduce the appearance of these lines, they do not address the underlying forces that cause these wrinkles to persist. Botulinum toxin type-A and type-B are neurotoxins that address these issues and result in the relaxation of the intrinsic facial muscles and subsequent resolution of these dynamic facial rhytides. This article will compare the efficacy, duration, dose ranging studies, and safety in the treatment of facial rhytides with both types of toxins. In addition, the treatment of hyperhidrosis with type-A and type-B botulinum toxin will also be discussed.
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Cosmeceuticals are skin care products that lie in a gray area between cosmetics and drugs. The desire for the improvement of aging skin has resulted in a plethora of products designed to improve the appearance beyond the simple camouflage of cosmetics. Many ingredients have been added to these products based on theoretical benefits discovered from in vitro studies on wound healing and other metabolic processes. To help the practicing dermatologist who is often the source of information for patients regarding the benefits of available cosmeceuticals. This article is a compilation of published studies on the effects and the practical applications of peptides as topical agents for skin improvement. There does seem to be science that shows that these peptide cosmeceuticals have the potential to improve the appearance of aging skin. It is important to remember, however, that for benefit to be realized, the final product must be stable in formula, absorbed into the skin, and biologically active at the target for clinical benefit. This article will provide dermatologists with more background to answer pressing questions from patients on this subject.
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Peptide cosmeceuticals are one of the new, popular options to treat aging skin. There are three main categories of cosmeceutical peptides: signal peptides, neurotransmitter-affecting peptides and carrier peptides. Although their benefits currently may not be as rigorously tested as most FDA-regulated drugs, the evidence to support their use is growing. This article attempts to review the various current popular cosmeceutical peptides, the published studies on their theoretical effects, and their practical use in dermatology.
Modulation of skin collagen metabolism in aged and photo aged human skin in vivo[J] Frolkis VV . Aging, anti-aging, ontogenesis and periods of age 9. development Differential 10. staining of collagen type I, II and III by Sirius red and polarization microscopy
  • Chung Jh Jy Seo
  • Choi
  • Hr
  • Mk Lee
  • Rhie G Youn Cs
Chung JH, Seo JY, Choi HR, Lee MK, Youn CS, Rhie G, 8. et al. Modulation of skin collagen metabolism in aged and photo aged human skin in vivo[J]. J Invest Dermatol. 2001 ; 117 : 1218. Frolkis VV. Aging, anti-aging, ontogenesis and periods of age 9. development[J]. Gerontology. 1999 ; 45 : 227. Junqueira LCU, Cossermlli W, Brentaini W. Differential 10. staining of collagen type I, II and III by Sirius red and polarization microscopy. Arch histol Jpn. 1978 ; 41 : 267 – 274.
Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and
  • J Varani
  • Rl M Warner
  • Phan
  • Sh
  • S Kang
  • Chung
  • Jh
Varani J, Warner RL, Gharaee-Kermnai M, Phan SH, Kang S, 16. Chung JH, et al. Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and
A peptide that mimics the arboxy-terminal domain of SNAP-25 blocks Ca2+-dependent exocytosis in chromaffin cells
  • L M Gutierrez
  • J M Cannes
  • A V Ferrer-Monteil
  • J A Reig
  • M Montal
  • S Viniegra