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Keywords = acetyl hexapeptide-8

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24 pages, 634 KB  
Perspective
Extracellular Matrix-Derived Matrikines: Circulating Peptides as Candidate Mediators of Lung-to-Brain Signaling
by Andis Klegeris
Int. J. Mol. Sci. 2026, 27(7), 3339; https://doi.org/10.3390/ijms27073339 - 7 Apr 2026
Cited by 1 | Viewed by 1038
Abstract
Recent studies support the concept of a bidirectional lung–brain axis. While neural, immune, and microbial pathways are increasingly recognized in lung-to-brain communication, the role of matrikines—bioactive peptides generated by extracellular matrix (ECM) proteolysis during remodeling—in this inter-organ communication remains underexplored. This review highlights [...] Read more.
Recent studies support the concept of a bidirectional lung–brain axis. While neural, immune, and microbial pathways are increasingly recognized in lung-to-brain communication, the role of matrikines—bioactive peptides generated by extracellular matrix (ECM) proteolysis during remodeling—in this inter-organ communication remains underexplored. This review highlights matrikines originating from the lung, particularly the collagen-derived tripeptide Pro-Gly-Pro (PGP) and the elastin-derived hexapeptide Val-Gly-Val-Ala-Pro-Gly (VGVAPG), as potential mediators linking pulmonary pathology with neurological outcomes. The lung is rich in ECM proteins, and inflammatory conditions such as chronic obstructive pulmonary disease (COPD) and emphysema trigger proteolytic activity by matrix metalloproteinases (MMPs) and neutrophil elastase, releasing matrikines into circulation. Under conditions of blood–brain barrier (BBB) dysfunction, they may access the central nervous system (CNS), where they influence neurons, microglia, and astrocytes, modulating neuroinflammation, autophagy, and synaptic integrity. While PGP can exhibit context-dependent neuroprotective effects, its acetylated form and VGVAPG are associated with neurotoxicity, Tau hyperphosphorylation, and microglial activation. Additional matrikines, including Gly-His-Lys (GHK) and endorepellin, may further modulate CNS homeostasis. Collectively, these findings support lung-derived matrikines as circulating mediators of lung-to-brain signaling, providing a novel mechanistic framework linking chronic pulmonary inflammation to neuropathologies, such as stroke and neurodegenerative disorders, and highlighting potential targets for therapeutic intervention. Full article
(This article belongs to the Section Macromolecules)
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12 pages, 228 KB  
Review
Acetyl Hexapeptide-8 in Cosmeceuticals—A Review of Skin Permeability and Efficacy
by Julita Zdrada-Nowak, Agnieszka Surgiel-Gemza and Magdalena Szatkowska
Int. J. Mol. Sci. 2025, 26(12), 5722; https://doi.org/10.3390/ijms26125722 - 14 Jun 2025
Cited by 6 | Viewed by 16899
Abstract
Biomimetic peptides represent a growing class of active ingredients in modern cosmeceuticals, designed to mimic the function of the naturally occurring peptides involved in skin homeostasis, repair, and regeneration. Among them, acetyl hexapeptide-8 (AH-8), often referred to as a “botox-like” peptide, has received [...] Read more.
Biomimetic peptides represent a growing class of active ingredients in modern cosmeceuticals, designed to mimic the function of the naturally occurring peptides involved in skin homeostasis, repair, and regeneration. Among them, acetyl hexapeptide-8 (AH-8), often referred to as a “botox-like” peptide, has received considerable attention for its potential to dynamically reduce wrinkles through the modulation of neuromuscular activity. AH-8 is widely used in topical formulations intended for anti-aging effects, scar treatment, and skin rejuvenation. This review provides a comprehensive overview of the structure and proposed mechanisms of action of AH-8, with particular focus on its efficacy and skin penetration properties. Due to its hydrophilic nature and relatively large molecular size, AH-8 faces limited permeability through the lipophilic stratum corneum, making effective dermal delivery challenging. Formulation strategies such as oil-in-water (O/W) and multiple water-in-oil-in-water (W/O/W) emulsions have been explored to enhance its delivery, but the ability of AH-8 to reach neuromuscular junctions remains uncertain. Preclinical and clinical studies indicate that AH-8 may reduce wrinkle depth, improve skin elasticity, and enhance hydration. However, the precise biological mechanisms underlying these effects—particularly the peptide’s ability to inhibit muscle contraction when applied topically—remain incompletely understood. In some studies, AH-8 has also shown beneficial effects in scar remodeling and sebum regulation. Despite promising cosmetic outcomes, AH-8’s low skin penetration limits its bioavailability and therapeutic potential. This review emphasizes the need for further research on formulation science and delivery systems, which are essential for optimizing the effectiveness of peptide-based cosmeceuticals and validating their use as non-invasive alternatives to injectable treatments. Full article
15 pages, 2546 KB  
Article
Unraveling the Molecular Mechanisms of Synthetic Acetyl Hexapeptide in E-Cadherin Activation for Tissue Rejuvenation
by Nikoleta Topouzidou, Androulla N. Miliotou, Danai Nodaraki, Eleftheria Galatou, Christos Petrou and Yiannis Sarigiannis
Cosmetics 2025, 12(2), 48; https://doi.org/10.3390/cosmetics12020048 - 12 Mar 2025
Cited by 1 | Viewed by 5319
Abstract
Objective: Dermo-cosmetics have significantly advanced, focusing on innovative and effective products such as cosmeceuticals—cosmetics infused with bioactive ingredients for skin benefits. Synthetic peptides are prominent among these bioactive molecules, noted for their enhanced effects in cellular processes related to skin physiology. Specifically, the [...] Read more.
Objective: Dermo-cosmetics have significantly advanced, focusing on innovative and effective products such as cosmeceuticals—cosmetics infused with bioactive ingredients for skin benefits. Synthetic peptides are prominent among these bioactive molecules, noted for their enhanced effects in cellular processes related to skin physiology. Specifically, the glycoprotein E-cadherin plays a crucial role in cellular adhesion and has shown promise in wound healing studies, although its broader cellular functions remain underexplored. Despite their widespread use, many cosmetic peptides lack genetic validation of their effects. This study focuses on the synthetic, amphiphilic acetyl hexapeptide-1, aimed to possess wound healing and anti-aging properties, with a novel exploration of its molecular mechanisms, specifically its effect on the expression of the CDH-1 gene, which encodes E-cadherin—a key protein in cellular adhesion and wound healing. Methods: In this investigation, the acetyl hexapeptide-1 was synthesized in house, followed by cell culture assessment and molecular evaluation. Human hepatocytes HepG2 were exposed to the synthetic hexapeptide to assess cytotoxic effects and examine its impact on gene expression, specifically targeting the wound healing-associated gene CDH-1, as well as apoptosis-related genes BAX, Bcl-2, Caspase-9, and Cyclin D1. Results: No cytotoxic effects were observed in cell cultures. Gene expression analysis revealed a significant increase in E-cadherin expression, along with the NO modulation of apoptosis-related genes (BAX, Bcl-2, Caspase-9) and the cell cycle-related gene Cyclin D1. These findings suggest peptide’s role in enhancing cellular adhesion, without any cytotoxic effects. Conclusions: The findings of this study provide promising insights into the potential molecular properties of synthetic acetyl hexapeptide-1, implying its applicability in cosmeceuticals. These cosmetic peptides hold enormous potential and diverse applications not only within skincare. To fully understand their benefits and expand their scope, additional investigations are warranted to comprehensively explore their molecular mechanisms across a spectrum of applications. Full article
(This article belongs to the Section Cosmetic Dermatology)
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11 pages, 1857 KB  
Article
Advancing Transdermal Delivery by Zn/Ag-Electrode-Printed Iontophoretic Patch with Self-Generating Microcurrents
by Cheng-Liang Peng, Pei-Chi Lee, Hsin-Tung Liu and Ping-Shan Lai
Sci. Pharm. 2024, 92(2), 26; https://doi.org/10.3390/scipharm92020026 - 14 May 2024
Cited by 1 | Viewed by 5788
Abstract
This study aimed to evaluate Zn/Ag-electrode-printed patches for the transdermal delivery of small molecules through iontophoresis. The Zn/Ag-electrode-printed patches interact with biological liquid electrolytes and generate suitable microcurrents for the iontophoretic delivery of small molecules across the skin. In fluorescein permeation studies, Zn/Ag-electrode-printed [...] Read more.
This study aimed to evaluate Zn/Ag-electrode-printed patches for the transdermal delivery of small molecules through iontophoresis. The Zn/Ag-electrode-printed patches interact with biological liquid electrolytes and generate suitable microcurrents for the iontophoretic delivery of small molecules across the skin. In fluorescein permeation studies, Zn/Ag-electrode-printed patches increased the transdermal depth of fluorescein into the dermis, while the permeation of fluorescein was limited when Zn/C-electrode-printed patches were tested. Further permeation experiments were conducted with 3D skin models, which showed a similar trend to the above, indicating that Zn/Ag-electrode-printed patches had a higher penetration rate compared to the blank. Studies using acetyl hexapeptide-8 as a peptide drug model and sodium ascorbyl phosphate (SAP) as a hydrophilic derivative of ascorbic acid showed that the iontophoretic patch with Zn/Ag electrodes promoted more penetration of drugs than unprinted patches. The permeation of SAP exhibited a two-phase profile with a relatively rapid permeation followed by a sustained, slower permeation. The permeation of acetyl hexapeptide-8 was slower due to its higher molecular weight, but the iontophoretic patch increased the permeation up to 1.5 times more than the unprinted patch. The microcurrent generated by the patch drives the transport of small molecule components through the skin, for the controlled and efficient delivery of therapeutic agents. The flexible design, efficient microcurrent generation, and stable electrodes make the Zn/Ag-electrode-printed patch a promising tool for transdermal drug delivery. Full article
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2 pages, 129 KB  
Abstract
Genetic Insights into E-Cadherin Modulation: Exploring the Benefits of Synthetic Acetyl Hexapeptide-1 in Wound Healing and Anti-Aging for Dermo-Cosmetics
by Nikoleta Topouzidou, Christos Petrou, Androulla N. Miliotou and Yiannis Sarigiannis
Proceedings 2024, 103(1), 48; https://doi.org/10.3390/proceedings2024103048 - 12 Apr 2024
Viewed by 2329
Abstract
Dermo-cosmetics are cosmetics combined with bioactive ingredients to impart therapeutic benefits on the skin and have made significant advances in recent decades [...] Full article
(This article belongs to the Proceedings of The 3rd International Electronic Conference on Biomolecules)
14 pages, 1880 KB  
Article
Peptide-Based Hydrogels and Nanogels Containing Gd(III) Complexes as T1 Relaxation Agents
by Elisabetta Rosa, Fabio Carniato, Lorenzo Tei, Carlo Diaferia, Giancarlo Morelli, Mauro Botta and Antonella Accardo
Pharmaceuticals 2022, 15(12), 1572; https://doi.org/10.3390/ph15121572 - 16 Dec 2022
Cited by 20 | Viewed by 3015
Abstract
New peptide-based hydrogels incorporating Gd(III) chelates with different hydration states, molecular structures and overall negative charges ([Gd(BOPTA)]2−), [Gd(DTPA)]2−, and ([Gd(AAZTA)]) were prepared and characterized. N-terminal Fmoc- or acetyl-derivatized hexapeptides (K1, K2 and K3) containing five aliphatic amino [...] Read more.
New peptide-based hydrogels incorporating Gd(III) chelates with different hydration states, molecular structures and overall negative charges ([Gd(BOPTA)]2−), [Gd(DTPA)]2−, and ([Gd(AAZTA)]) were prepared and characterized. N-terminal Fmoc- or acetyl-derivatized hexapeptides (K1, K2 and K3) containing five aliphatic amino acids (differently ordered Gly, Ala, Val, Leu and Ile) and a charged lysine at the amidated C-terminal were used for the formation of the hydrogels. Particular attention was paid to the investigation of the morphological and rheological properties of the nanoparticles, in addition to the assessment of the ability (relaxivity) of the confined complexes to accelerate the longitudinal relaxation rate of the water protons localized in the polymeric network. The relaxivity values at high magnetic fields (>0.5 T) of the paramagnetic hydrogels appear to be more than five times higher than those of isolated chelates in an aqueous solution, reaching a value of 25 mmol−1 s−1 for Fmoc-K2+[Gd(BOPTA)]2− at 0.5 T and 310 K. Furthermore, an interesting trend of decrease of relaxivity with increasing the degree of rigidity of the hydrogel was observed. The type of interactions between the various complexes and the polymeric network also plays a key role in influencing the relaxivity values of the final materials. Nanogels were also obtained from the submicronization of the hydrogel containing [Gd(BOPTA)]2− chelate. Circular dichroism, dynamic light scattering and relaxometric investigations on these nanoparticles revealed the formation of nanogels endowed with higher relaxivities (r1 = 41 mM−1 s−1 at 0.5 T MHz and 310 K) than the corresponding hydrogels. Full article
(This article belongs to the Special Issue Molecular Systems for the Delivery of Drugs and Contrast Agents)
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11 pages, 2032 KB  
Article
Quantitation of Acetyl Hexapeptide-8 in Cosmetics by Hydrophilic Interaction Liquid Chromatography Coupled to Photo Diode Array Detection
by Vasiliki Raikou, Eleni Kalogria, Athanasia Varvaresou, Efthimios Tsirivas and Irene Panderi
Separations 2021, 8(8), 125; https://doi.org/10.3390/separations8080125 - 18 Aug 2021
Cited by 12 | Viewed by 15179
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Collection State of the Art in Separation Science)
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22 pages, 2024 KB  
Review
Usage of Synthetic Peptides in Cosmetics for Sensitive Skin
by Diana I. S. P. Resende, Marta Salvador Ferreira, José Manuel Sousa-Lobo, Emília Sousa and Isabel Filipa Almeida
Pharmaceuticals 2021, 14(8), 702; https://doi.org/10.3390/ph14080702 - 21 Jul 2021
Cited by 39 | Viewed by 20309
Abstract
Sensitive skin is characterized by symptoms of discomfort when exposed to environmental factors. Peptides are used in cosmetics for sensitive skin and stand out as active ingredients for their ability to interact with skin cells by multiple mechanisms, high potency at low dosage [...] Read more.
Sensitive skin is characterized by symptoms of discomfort when exposed to environmental factors. Peptides are used in cosmetics for sensitive skin and stand out as active ingredients for their ability to interact with skin cells by multiple mechanisms, high potency at low dosage and the ability to penetrate the stratum corneum. This study aimed to analyze the composition of 88 facial cosmetics for sensitive skin from multinational brands regarding usage of peptides, reviewing their synthetic pathways and the scientific evidence that supports their efficacy. Peptides were found in 17% of the products analyzed, namely: acetyl dipeptide-1 cetyl ester, palmitoyl tripeptide-8, acetyl tetrapeptide-15, palmitoyl tripeptide-5, acetyl hexapeptide-49, palmitoyl tetrapeptide-7 and palmitoyl oligopeptide. Three out of seven peptides have a neurotransmitter-inhibiting mechanism of action, while another three are signal peptides. Only five peptides present evidence supporting their use in sensitive skin, with only one clinical study including volunteers having this condition. Noteworthy, the available data is mostly found in patents and supplier brochures, and not in randomized placebo-controlled studies. Peptides are useful active ingredients in cosmetics for sensitive skin. Knowing their efficacy and synthetic pathways provides meaningful insight for the development of new and more effective ingredients. Full article
(This article belongs to the Special Issue New Applications and Developments in Synthetic Peptide Chemistry)
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15 pages, 1138 KB  
Article
Trending Anti-Aging Peptides
by Marta Salvador Ferreira, Maria Catarina Magalhães, José Manuel Sousa-Lobo and Isabel Filipa Almeida
Cosmetics 2020, 7(4), 91; https://doi.org/10.3390/cosmetics7040091 - 14 Nov 2020
Cited by 72 | Viewed by 59591
Abstract
The development of synthetic peptides for skin care dates to the 1980s. The cosmetic industry periodically launches new peptides, as they are promising and appealing active ingredients in the growing and innovative cosmetics market. In this study, trends in the use of peptides [...] Read more.
The development of synthetic peptides for skin care dates to the 1980s. The cosmetic industry periodically launches new peptides, as they are promising and appealing active ingredients in the growing and innovative cosmetics market. In this study, trends in the use of peptides in anti-aging products were analyzed by comparing the composition of the products marketed in 2011 with products launched or reformulated in 2018. The scientific and marketing evidence for their application as active ingredients in anti-aging cosmetics was also compiled from products’ labels, suppliers’ technical data forms and online scientific databases. The use of peptides in anti-aging cosmetics increased by 7.2%, while the variety and the number of peptide combinations in products have increased by 88.5%. The most used peptides in antiaging cosmetic formulations are, in descending order, Palmitoyl Tetrapeptide-7, Palmitoyl Oligopeptide and Acetyl Hexapeptide-8. In 2011, the majority of peptides were obtained from synthesis, while in 2018, biotechnology processing was the dominant source. This study provides an overview of the market trends regarding the use of peptides in anti-aging products, providing meaningful data for scientists involved in the development of new peptides to identify opportunities for innovation in this area. Full article
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2020)
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22 pages, 3934 KB  
Article
N-Terminal Acetylation and C-Terminal Amidation of Spirulina platensis-Derived Hexapeptide: Anti-Photoaging Activity and Proteomic Analysis
by Qiaohui Zeng, Jianguo Jiang, Jingjing Wang, Qiuchan Zhou and Xuewu Zhang
Mar. Drugs 2019, 17(9), 520; https://doi.org/10.3390/md17090520 - 4 Sep 2019
Cited by 21 | Viewed by 5274
Abstract
Ultraviolet (UV) irradiation is a potent inducer for skin photoaging. This paper investigated the anti-photoaging effects of the acetylated and amidated hexapeptide (AAH), originally identified from Spirulina platensis, in (Ultraviolet B) UVB-irradiated Human immortalized keratinocytes (Hacats) and mice. The results demonstrated that [...] Read more.
Ultraviolet (UV) irradiation is a potent inducer for skin photoaging. This paper investigated the anti-photoaging effects of the acetylated and amidated hexapeptide (AAH), originally identified from Spirulina platensis, in (Ultraviolet B) UVB-irradiated Human immortalized keratinocytes (Hacats) and mice. The results demonstrated that AAH had much lower toxicity on Hacats than the positive matrixyl (81.52% vs. 5.32%). Moreover, AAH reduced MDA content by 49%; increased SOD, CAT, and GSH-Px activities by 103%, 49%, and 116%, respectively; decreased MMP-1 and MMP-3 expressions by 27% and 29%, respectively, compared to UVB-irradiated mice. Employing isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics, 60 differential proteins were identified, and major metabolic pathways were determined. Network analysis indicated that these differential proteins were mapped into an interaction network composed of two core sub-networks. Collectively, AAH is protective against UVB-induced skin photoaging and has potential application in skin care cosmetics. Full article
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7 pages, 589 KB  
Article
The Efficiency and Safety of Leuphasyl—A Botox-Like Peptide
by Anca O. Dragomirescu, Mihaiela Andoni, Daniela Ionescu and Felicia Andrei
Cosmetics 2014, 1(2), 75-81; https://doi.org/10.3390/cosmetics1020075 - 8 Apr 2014
Cited by 16 | Viewed by 24520
Abstract
Peptides of synthesis are a very new strategy in cosmetic science and technology for at least two reasons: (1) they are small molecules, easily penetrable in the skin and (2) they are able to induce a very specific action, because all skin cells [...] Read more.
Peptides of synthesis are a very new strategy in cosmetic science and technology for at least two reasons: (1) they are small molecules, easily penetrable in the skin and (2) they are able to induce a very specific action, because all skin cells (keratinocytes, fibroblasts, nervous cells) have membrane receptors for peptides. This group of cosmeceutics includes the botox-like peptides, represented by acetyl hexapeptide 3 (Argireline) and pentapeptid-3 (Leuphasyl). The latter is less known and has been less studied. This substance inhibits the neuromuscular synapses in the mimic muscles, acting as enkephalins. It links the enkephalin receptor to nervous cells, thereby modulating the release of acetylcholine in synaptic space. This cellular activity will be translated in vivo in a relaxation of the muscle and a reduction of expression wrinkles. The aim of our study is to evaluate the optimal concentration of Leuphasyl for skin application at the mimic muscle level, the efficiency and the safety of this peptide. We formulated three emulsions of different concentrations (0.5%, 1%, 2%) which were applied to the skin, at the level of mimic muscles (1) at the eyebrows zone (above the corrugator supercilii muscle) and (2) at the periorbital zone (above the orbicularis oculi muscle). We evaluated the regression of the wrinkles between the eyebrows using an imagistic method: pro-derm Analyser. The study is of interest to discussions concerning how to apply these kinds of cosmetic products at the mimic muscle skin level and not at the level of the wrinkles. Full article
(This article belongs to the Special Issue Selected Papers from ISBS/SICC 1st Joint International Congress)
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