Cosmetic Peptides

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Aging is a natural process in human life, indicating the gradual decay of organisms. With the increasing longevity of the population worldwide, good appearance of aged skin is essential to a better quality of life for people in advanced age, with more independence and sometimes with intense professional and social activity. Scientific literature reports that some peptides can act as cellular messengers. These peptides are capable to incite both collagen production and to regulate the enzyme collagenase involved in collagen degradation.

Bioactive peptides, typically consisting of 3-30 amino acids (AAs), are derived from natural proteins. These peptides serve as signal molecules to trigger cascade reactions or as substrates involved in biological activities. In the last 50 decades, the application of bioactive peptides has been continuously extended in the field of cosmetics. Cosmetic peptides typically contribute to the augmentation of skin cell viability and proliferation, the reduction of skin pigmentation, the mitigation of tissue inflammation, the enhancement of skin barrier functionality, and the provision of support to the skin.

Characteristics of Cosmetic Peptides

Cosmetic peptides should have the following characteristics simultaneously:

  • Given the specific amino acid sequence and molecular weight, the common cosmetic peptides at present are 2-10 amino acid condensates.
  • The mechanism is clear, and it clearly acts on a micro receptor of the skin.
  • The addition amount is small, a few ppm- several hundred ppm will have obvious effect.

Classification of Cosmetic Peptides

A variety of peptides are used in cosmetics. According to their mode of action, they have been classified into four main groups: signal peptides, carrier peptides, neurotransmitter peptides and enzyme inhibitor peptides.

Signal Peptides

Signal peptides can promote the synthesis of matrix proteins, especially collagen, and may also increase the production of elastin, hyaluronic acid, glycosaminoglycans, and fibronectin. This type of peptide promotes collagen synthesis by increasing stromal cell activity, making the skin appear more elastic and youthful. The function of palmitoyl oligopeptide (palmitoyl tripeptide-1) is basically the same, which is also the reason why palmitoyl oligopeptide is widely used. Common commercially available palmitoyl pentapeptide-3 (Matrix), palmitoyl tripeptide-1 (Matrix 3000), palmitoyl hexapeptide-EL, palmitoyl tripeptide-5, hexapeptide-9, and myristoyl pentapeptide-11 are all signaling peptides.

Carrier Peptides

This type of peptide is represented by coppertripeptide. The tripeptide Gly-L-His L-Lys (GHK) in human plasma has a strong affinity for divalent copper ions and can spontaneously form complex copper peptides (GHK-Cu). Copper is a trace element required to maintain bodily functions (2 milligrams per day), with many and complex functions. It is an element required for various cellular enzymes. In terms of skin tissue function, it has the functions of antioxidant, promoting collagen proliferation, and assisting wound healing. The wrinkle removal effect of copper is mainly carried by peptide carriers, allowing divalent copper ions with biochemical effects to enter cells and exert physiological functions. GHK-Cu can effectively promote the generation of collagen and elastin proteins, increase vascular growth and antioxidant capacity, and stimulate the production of glucopolyamine (GAGs) to help the skin repair itself.

Neurotransmitter-Inhibitor Peptides

This type of peptide is a botulinum toxin like mechanism that inhibits the synthesis of SNARE receptors, inhibits the excessive release of catecholamines and acetylcholine in the skin, locally blocks nerve transmission of muscle contraction signals, relaxes facial muscles, and achieves the goal of smoothing fine lines. This type of peptide, like signal peptides, is widely used and particularly suitable for areas with concentrated facial expressions (corners of the eyes, face, forehead). Representative peptide products include: acetyl hexapeptide-3 (Argireline), acetyl octapeptide-1 (Snap-8), pentapeptide-3 (Pentapeptide-3), dipeptide snake venom, and pentapeptide-3.

Enzyme-Inhibitor Peptides

Enzyme inhibitor peptides inhibit the efficiency of a key enzyme in some processes of metabolism. Many of the enzyme inhibitor peptides are extracted from botanical sources. Some peptides derived from rice proteins work well to retain more collagen, while certain soy-derived peptides can help prevent pigmentation.

Mechanisms of Action of Bioactive Peptides

Bioactive peptides, with their powerful single/multifunctional biological properties (e.g., antimicrobial, antioxidant, anti-aging, and anti-inflammatory activities) have been widely applied as functional ingredients in the dermatology and cosmetology fields. The peptides can improve skin health in a number of aspects, including extracellular matrix synthesis, innate immunity, inflammation, and pigmentation.

Bioactive Peptides with Anti-Aging Properties

During the intrinsic or chronological aging, alterations occur on the biosynthetic activity of skin-derived cells such as collagen, elastin, and hyaluronic acid, as well as a simultaneously overproduction of several skin enzymes, called aging-related enzymes (e.g. elastase, collagenase and hyaluronidase) that are implicated in the degradation of the protein matrix of the skin. Anti-skin aging properties are related to the inhibition of key physiological enzymes such as elastase, collagenase, tyrosinase, and hyaluronidase.

  • Collagenase Inhibition

Inhibits mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF- κB) signaling pathways, and histone modification. Suppresses the activities and expressions of MMP by elevating tissue inhibitors of matrix metalloproteinases (TIMP) levels and blocking activation of MAPK signaling pathway.

  • Hyaluronidase Inhibition

Inhibits the degradation of hyaluronic acid for protecting skin.

  • Elastase Inhibition

Downregulates the activation of elastase enzyme to protect mechanical properties of skin tissues that are impaired by overproduction of the enzyme elastase.

Peptides with Anti-Pigmentation Properties

Melanin is the major pigment responsible for skin color. However, when there is an overproduction of tyrosinase, which is responsible for melanin production, it causes skin hyperpigmentation that leads to a darker skin appearance such as light to dark brown spots, irregular grey patches on the face, neck and trunk, and pale brown to dark brown spots on the skin. Tyrosinase is an enzyme that contains copper in its active site for catalyzing the oxidation reaction; therefore, bioactive compounds that block the active site or chelate copper ions can be used to inhibit this enzyme.

  • Tyrosinase Inhibition

Blocks the active site or chelates copper ions of tyrosinase to inhibit tyrosinase activity. Downregulates the activation of microphthalmia-associated transcription factor (MITF), an important event during melanogenesis, to suppress melanin synthesis. Downregulates cAMP signaling pathway as an anti-melanogenic activity to inhibit melanin synthesis

Peptides with Antimicrobial Activity

The skin, as the outmost barrier of our body, is constantly exposed to microbial agents and therefore there is a loss of the skin's antimicrobial function (i.e. the cutaneous production of antimicrobial peptides in response to microbial invasion) with aging. Some microorganisms are related to skin diseases, such as Staphylococcus aureus in atopic dermatitis and Propionibacterium acnes in acne vulgaris. Using bioactive peptides with antimicrobial activity against these microorganisms are promising functional ingredients in topical applications of cosmeceuticals. In addition, bioactive peptides are considered as a potential alternative to antibiotic treatments in acne vulgaris because the development of a resistant strain of Propionibacterium acnes has become problematic.

  • Provide antimicrobial activity based on membrane lytic mechanisms whereby peptides can directly affect cell membrane integrity through the formation of transmembrane channels, resulting in cytoplasm leakage and cell death.
  • Involved with the inhibition of intracellular activities in nucleic acid, protein and cell-wall synthesis, protein folding, lipopolysaccharide formation, and cell-division progress.
  • Induce a loss of regulated iron transport, leading to membrane permeation and DNA damage, and subsequently to bacterial destruction.

Peptides with Antioxidant Activity

During long-term exposure of skin to ultraviolet (UV) radiation or exposure to xenobiotic compounds with oxidative reactions (e.g. solvents, toxins), there is an excessive production of reactive oxygen species (ROS), triggered in oxidative stress, which is implicated in the pathogenesis of dermatologic diseases, including skin cancer. Bioactive peptides with antioxidant properties may be used to prevent the deleterious effect of oxidative stress occasioned by the excessive production of ROS in the skin.

  • Prevent the deleterious effects of oxidative stress caused by overproduction of ROS in the skin.
  • Act as antioxidants through hydrogen atom transfer, single electron transfer, and chelating transition pro-oxidant metals.

Peptides with Anti-Inflammatory Activity

It has been reported that inflammation contributes to aging and age-related diseases, because continuous (chronic) upregulation of pro-inflammatory mediators is induced during the aging process as a result of an age-related redox imbalance and dysregulation of the immune system that activates many pro-inflammatory signaling pathways. Furthermore, it has been reported that some skin diseases such as atopic dermatitis, xerosis, rosacea and psoriasis are classified as chronic inflammatory diseases. The anti-inflammatory mechanisms of bioactive peptides are related to their capacity to bind to the lipid A moiety of LPS and the interference with LPS-CD14 interactions by means of competition with the LPS-binding peptide.

  • Possesses anti-inflammatory capacity mediated by the inhibition and induction of the immune systems in cell lines.
  • Downregulates pro-inflammatory mediators (e.g., TNF-α, IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-12, and IFN-γ receptors) and regulates immune system.

Fig. 1 Schematic summary of the mechanisms of bioactive peptides related to their potential cosmeceutical application.Fig. 1 Schematic summary of the mechanisms of bioactive peptides related to their potential cosmeceutical application. (Aguilar-Toalá, J. E., 2019)

Natural Sources of Bioactive Peptides

Bioactive peptides with promising cosmetic properties come from different sources, including chemical synthesis and natural sources. Chemical synthesis involves using a mixture of amino acids as a starting material, allowing peptides of different amino acid sequences and combinations to be obtained. Natural sources, such as plants, animals, and marine sources, can be used to extract bioactive peptides using various approaches (e.g., enzymatic hydrolysis, microbial fermentation, chemical digestion, high-performance liquid chromatography (HPLC), electro-membrane fractionation by electrodialysis with ultrafiltration, cell filtration chromatography, and recombinant production). The diversity of natural sources is expected to produce a wide range of desirable functional peptide structures.

Plant Sources

Bioactive peptides with antioxidant and antimicrobial activities are expected to provide great cosmetic benefits. Common antimicrobial peptides comprise thionins, defensins, 2S albumin-like proteins, cyclotides, and lipid transfer proteins, of which thionins are the first identified to play a significant role in protecting plants against invading bacteria. The antimicrobial properties help peptides penetrate the bacterial membrane, then create pores and eliminate the bacteria by altering their homeostasis. Additionally, plant-derived peptides are also toxic to a variety of Gram-negative and Gram-positive bacteria, and even mammalian bacteria.

Animal Sources

Animal-derived peptides are also increasingly attracting interest as prominent candidates in the field of cosmetology. It has been reported that peptides of animal origin can lower blood pressure, stimulate the immune system, inhibit proline-specific endopeptidase activity, induce smooth muscle contraction, have antibacterial and antimicrobial activities, and improve the nutritional value of foods.

Marine Sources

Marine-based peptides exhibit various bioactivities including antioxidant, neuroprotective, antidiabetic, immunomodulatory, antibacterial, antiproliferative, and antioxidant activities. For instance, the Porphyra dioica algae were used to extract eight peptide sequences through enzymatic hydrolysis and reverse-phase HPLC approaches. Among the derived peptides, the Asp-Tyr-Tyr-Lys-Arg sequence exhibited the highest antioxidant activity and the Tyr-Leu-Val-Ala sequence showed dipeptidyl peptidase IV (DPP-IV) inhibitory activities, while the Thr-Tyr-Ile-Ala peptide had the highest angiotensin-converting enzyme (ACE) inhibitory activity. It can be seen that these peptides have potential applications as ingredients to improve health and skin appearance.

Edible Insect Sources

Edible insects have been considered as new sources of peptides based on their good source of protein. Insect-derived bioactive peptides are characterized by a variety of properties such as antioxidant, anti-inflammatory, antidiabetic, antimicrobial, and ACE-inhibitory activities. For instance, Zielinska et al. successfully identified antioxidant and anti-inflammatory peptides through stimulation of the gastrointestinal digestion of three edible insects (Schistocerca gregaria, Tenebrio Molitor, and Gryllodes Sigillatus).

Application of Cosmetic Peptides

Anti-Aging Treatments: Peptides stimulate the production of collagen and downregulate the activation of elastase to protect the mechanical properties of skin tissue damaged by overproduction of the enzyme elastase, thereby improving elasticity, reducing wrinkles and fine lines, and restoring the youthful appearance of skin.

Anti Pigmentation: Peptides consisting of amino acids with hydroxyl groups (Ser and Thr), aliphatic amino acid residues (Val, Ala, and Leu), and hydrophobic compounds exhibit great tyrosinase inhibitory activities, thus inhibiting melanin formation.

Wound Healing: Some peptides such as Copper peptides promote skin regeneration and wound healing by promoting collagen production, attracting immune cells, and acting as antioxidants.

Hair Growth Products: There are certain types of peptides that have been shown to stimulate hair growth and reduce hair loss.

Moisturizing Products: Hydrating peptides lock in moisture and help the skin to retain it, resulting in a plumped and hydrated complexion.

Reducing Inflammation: Peptides like azelaic acid can reduce inflammation, redness, and irritation in the skin, making these peptides particularly useful in products for sensitive skin and in treating certain skin conditions like rosacea.

Targeted Treatments: Due to their small size, peptides can penetrate the skin's surface especially when encapsulated or carrier-enhanced, making them useful in targeted treatments like under-eye creams or serums.

Antimicrobial Peptides: There are peptides with antimicrobial properties, these can be used in products targeting acne-prone skin, as they may help kill acne-causing bacteria.

Creative Peptides is able to provide a wide range of bioactive cosmetic peptides and also advisory services regarding cosmetic formulation. We will always endeavor to offer you the BEST QUALITY peptides. We can offer research- and GMP-grade cosmetic peptides according to your exact specifications. Please check our list of some of the most popular cosmetic peptides standing by. If you have a different cosmetic peptide synthesis requirement in mind, please let us know the peptide sequence, purity level required, and quantity needed. Our sales team will quickly generate a quote for you with price and delivery time.

Case Study

Case Study 1

In this study, two novel targeting peptide motifs were designed to enhance the interaction between cosmetic peptides and the cell surface, thereby improving their performance for skin health. To achieve this, the well-known peptide tripeptide-1 (GHK) was optimized by separately grafting the integrin αvβ3-binding motif RGD and the chondroitin sulfate (CS)-binding motif sOtx2 onto it, forming two chimeric targeting peptides, RGD-GHK and sOtx2-GHK. Comparative analysis showed that both RGD-GHK and sOtx2-GHK exhibited superior anti-oxidative and anti-apoptotic effects compared to the non-targeting peptide, GHK. Furthermore, RGD-GHK demonstrated exceptional anti-aging activity, and its potential for promoting wound healing and repairing the skin barrier was evaluated in vitro using cells and skin models. In vitro permeation and in vivo adsorption testing confirmed that RGD-GHK achieved a high local concentration in the skin layer, initiating peptide effects and facilitating in vivo wound healing, while maintaining excellent biocompatibility. The enhancement of signaling cosmetic peptides can be attributed to the specific interaction between the binding motif and cell surface components. Consequently, this targeting peptide holds promising potential as a novel functional peptide for application in cosmetics.

Fig. 2 Anti-senescent effect of peptides on H2O2-induced HFF-1 and NIH3T3.Fig. 2 Anti-senescent effect of peptides on H2O2-induced HFF-1 and NIH3T3. (He, B., 2023)

References

  1. Aguilar-Toalá, J. E., et al. Potential role of natural bioactive peptides for development of cosmeceutical skin products. Peptides. 2019, 122: 170170.
  2. Ngoc, L. T. N., et al. Insights into Bioactive Peptides in Cosmetics. Cosmetics. 2023, 10(4): 111.
  3. He, B., et al. Role of peptide–cell surface interactions in cosmetic peptide application. Frontiers in Pharmacology. 2023, 14: 1267765.
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