Bioactive Peptides

The more we know about skin and its aging, the better technologies we can develop to positively affect it. Retinol was first used in skin care in the 1970s; since then, it has been further developed in a wide variety of ways to be used specifically to reduce aging changes or alleviate acne. In the 1970s, scientists laughed at the idea that free radicals could cause damage to the skin and accelerate its aging. Today, it has been proven that quite a few antioxidants protect the skin from the destructive effects of free radicals. Recently, stem cells from a Swiss apple variety found their way into cosmetics, and they were followed by a handful of other rejuvenating plant stem cells.
We are also witnessing continuous technological developments in bioactive peptides. Scientists knew about peptides as early as the 1950s, but it was not until the late 1980s that the first copper peptides were used in skin care. Then it took until the early 2000s before palmitoyl pentapeptide was discovered as an irritation-free alternative to retinol with comparable anti-aging effects. These peptides paved the way for other peptides that eventually established a category in their own right and surpassed the first generation in their collagen-strengthening effects.

Bioactive peptides and proteins in the skin

Skin aging involves a number of complex factors:

• Increase in proteolytic activity that occurs when proteins are degraded;
• Increase in free radical damage. These lead to chain reactions of inflammation and the destruction of cells.
• Decrease in communication between growth factors and cells, eventually leading to decrease in structural proteins;
• Weakening of the dermis-epidermal junction (DEJ).

These changes cause the skin to lose its suppleness, firmness, smooth surface, even pigmentation and elasticity. The development of bioactive peptides can be the answer to such skin problems and thus slow down skin aging.

Peptides are active protein-forming amino acid chains. Proteins are vital elements for every organism and are involved in almost all processes in the cells. They play an important role in regulating bodily functions, fighting inflammation, and curbing harmful oxidation processes. If we can decipher the multiple roles that proteins play in the body, we can harness bioactive peptides. Thanks to technological advances, topically applied peptides can more specifically address skin problems. When certain bioactive peptides are applied to the skin, the skin receives, so to speak, a protein-rich diet that strengthens and orders its restorative elements and provides it with the nutrients necessary for a strong, healthy structure.

The skin

Proteins are present in the skin in various forms and perform many tasks. The uppermost layers of the skin are similar to a wall made of bricks and mortar. Here, the keratinized cells (corneocytes) – comparable to bricks – are connected by desmosomes and held together by lipids (mortar). Peptides modified with a fatty acid component can be easily absorbed into the skin.

Dermis-Epidermis Junction (DEJ): The DEJ holds the skin together and provides a compact, firm and elastic structure.  Through it, the epidermis and dermis are interlocked, much like chain links. If only one link breaks, it affects elasticity and the skin becomes loose and saggy.

Extracellular Matrix (ECM): The ECM is a complex network of proteins and proteoglycans that can interact with multiple receptors on the cell surface simultaneously. These proteins include a variety of different collagens, laminins, fibronectins and elastins that are essential for cell growth and wound healing.

Collagen: The function of collagen can be thought of as similar to the function of the springs in a mattress. It is a supporting framework in the skin. When it becomes weak or is no longer produced in sufficient quantities, wrinkles appear. It is the protein with the highest content in the ECM. Around the age of 35, the decrease of type I and type III collagen becomes visible with the appearance of fine lines and wrinkles; however, the decrease of other types of collagen also contributes to the formation of wrinkles. To date, 29 types of collagen have been identified; and more are being discovered all the time. Collagen is not only responsible for the youthful appearance of the skin. It is also a component of ligaments and connective tissue.
The types of collagen found in the skin are divided into five families according to their structural type: Fibrils (type I, II, III, V, XI), FACIT (type IX, XII, XIV), Short-chain (type VIII, X), Basement membrane (type IV), and Other (type VI, VII, XIII).

Other building blocks in the skin matrix: The impact of collagen depletion is becoming better understood as anti-aging skin care is developed. However, other proteins are also critical in reducing fine lines and wrinkles.

• Laminin (including laminin V): The second most abundant protein in the ECM, it is found only in the basement membrane, which is a support structure of the epidermis. It provides support to the epidermis and connects it to the dermis.
• Elastin: This protein is found in connective tissue. It gives elasticity to the tissue and allows it to stretch.
• Integrins are cell membrane proteins. These mediate the attachment of cells to ECM proteins, such as collagen and laminin.
• Fibronectin: The protein binds cells to collagen and improves cell adhesion to collagen and cell membrane integrin.
• Decorin (proteoglycan): The glycosylated protein (a protein bound to a carbohydrate) plays an important role in cell-to-cell adhesion, acts as a filler, is significant for protein stability and cell signaling.
• Hyaluronic acid: The glycosaminoglycan is located in the extracellular space, which is resistant to deformation by absorbing large amounts of water.

How bioactive peptides work

Simply put, peptides behave like messengers that signal cells to perform specific functions, such as forming or inhibiting enzymes. One of the first peptides used on a larger scale, palmitoyl pentapeptide, is a collagen fragment that causes the increase of collagen I, IV and glycosaminoglycans. The collagen fragment causes the skin to assume that too much collagen has been broken down by natural degradation processes; thus, it triggers an increase in collagen synthesis. Although the peptide has been shown to be effective in stimulating collagen formation, it addresses only one aspect in the repair of the building blocks of the skin. Since the introduction of this peptide, the category of bioactive peptides has grown to offer a broad spectrum for use in skin care. Bioactive peptides today take a multifunctional approach to the task, improving skin appearance and feel in the following six aspects:

• Cleansing: Exfoliating, clarifying, removing impurities and residues from the skin.
• Relax: Minimize the repetitive contractions of facial muscles that cause wrinkles.
• Nourish: Providing the skin with essential nutrients, vitamins, and energy.
• Stimulate: Promote healthy skin functions.
• Moisture: Ensure perfectly balanced hydration, moisturize the skin.
• Protect: Maintain a healthy collagen matrix and strengthen the skin’s defenses.

Initially, externally applied peptides were primarily intended to help stimulate collagen and relax expression lines. In the meantime, numerous innovations have expanded their spectrum of action. The first generation peptides supported one or two types of collagen. However, as mentioned earlier, there are many types of collagen and the structure of DEJ depends on each collagen type being present in the right quality and quantity. Peptides have evolved. In fact, second and third generation bioactive peptides are replacing many controversial agents and providing efficient and tolerable alternatives.

Peptides that cleanse:

Peptides with exfoliating effect that do not irritate the skin:

• Hexanoyl dipeptide-3-norleucine acetate – The amino acid sequence restores uniform desquamation by displacing desmosomes. Desmosomes (desmoglein and desmocollin) are adhesion proteins that hold skin cells together and are thus significant in desquamation. The chain of three amino acids is perceived to be identical to desmoglein at the binding site of desmocollin; but instead of holding cells together, it weakens the connection between cells. The hydration of the skin improves, its surface becomes smoother, the depth of wrinkles decreases.

Peptides as alternatives to sulfate-containing foaming agents:

• Hydrolyzed Amaranth Protein – Organic-based cleansing substance effectively removes dirt and oily residues while moisturizing and providing irritation-free, rich lather. Amaranth is a flowering pseudocereal that grows 1.5 to 2 meters high. The Aztecs attributed supernatural powers to it. Amaranth contains a high concentration of nine essential amino acids that promote wound healing, boost skin functions and support antioxidation.

Peptides for the correction of acne:

• Oligopeptide-10 – The antimicrobial peptide is effective against acne. Used alone, it has been proven to fight the acne propionibacterium. In combination with weakly concentrated salicylic acid, it is even more effective. In this way, the pores are opened, allowing oxygen to penetrate and Oligopeptide-10 to enter the pores and exert its intense efficacy without causing irritation. A combination of 0.5% Oligopeptide-10 with 0.5% Salicylic Acid reduces blackheads, irritation, pustules and cysts 40% more effectively than a leading brand’s benzoyl peroxide preparation within 28 days.

Bioactive peptides that relax:

Facial expressions are formed by contractions of the muscles under the skin. Because the skin is connected to these muscles and such movements are frequently repeated, facial expression lines eventually develop. Muscle contraction is a complex mechanism based on numerous pathways at the motor endplate (neuromuscular junction / NMJ). The presynaptic and postsynaptic phases must be distinguished. Acetylcholine (ACh) is required for muscle contraction to occur. If the release of ACh at the NMJ or the uptake of ACh through various channels is blocked, lines can be smoothed and the formation of wrinkles prevented from the outset. In this context, the term “Botox-like” peptide was introduced years ago. What was meant was Argireline, which blocks the release of ACh right from the start. Meanwhile, relaxing bioactive peptides reduce wrinkle formation with higher efficacy.

• Acetyl Octapeptide-3 – The extended Argireline formula blocks the SNARE complex more efficiently. By blocking the formation of the SNARE complex in the presynaptic membrane, the release of ACh is minimized, reducing wrinkle-forming contractions and softening expression lines.
• Dipeptide diaminobutyrolyl benzylamide diacetate – It reduces ACh binding at the postsynaptic membrane by acting as an antagonist of the muscle nicotinic acetylcholine membrane receptor (mnAChR). This reduces sodium (Na+) uptake and consequently relaxes muscle contraction and attenuates writhing.
• Hydrolyzed Hibiscus Fruit Extract – Oligopeptide derived from okra has been shown to decrease the release of ACh and also exerts antioxidant protective effects by activating glutathione.

Bioactive peptides that nourish:

• Hexapeptide-11 – The four-amino acid peptide has a positive regulatory effect on: Transmembrane proteins, growth factors, matrix proteins, formation of skin lipids, cell stress.
• Peptides nourishing with colostrum-like peptides:
  o Whey protein – It contains a network of signal peptides of active milk, such as lactoglobulin, lactalbumin, lactoferrin, lactose and other carriers that activate cell metabolism and stimulate such proteins as collagen I. This peptide has been shown to stimulate cell migration and TGF-ß for faster wound healing.

Bioactive peptides that stimulate:

•  Palmitoyl oligopeptide and palmitoyl tetrapeptide-3 – The compound of cell communication peptides can regulate cell activities involved in ECM renewal of collagen I, fibronectin, and hyaluronic acid.
• Palmitoyl tripeptide-5 – The multifunctional protein activates the formation of collagen I by means of TGF-ß. Studies have shown that it is more effective than palmitoyl pentapeptide.

Peptides that improve the dermis-epidermis junction (DEJ):

• Palmitoyl dipeptide-5 diaminobutyloyl hydroxythreonline and palmitoyl dipeptide-6 diaminohydroxybutyrate – They stimulate the main protein structures in DEJ (laminin V, collagen IV, VII, XVII and integrin). This improves communication and nutrient supply, which in turn leads to the reduction of wrinkles, tissue restructuring, and thus improves skin firmness.

 Peptides that have a positive effect on the skin around the eyes:

• Palmitoyl Oligopeptide and Palmitoyl Tetrapeptide-3 – The combination of the two peptides improves firmness and tone and eliminates dark circles resulting from the accumulation of the pigment bilirubin in the blood.
• Hydrolyzed Rice Protein, Oxidoreductases and Soy Protein – The trifecta of plant and yeast peptides improves tissue oxygenation and promotes fibroblast formation. Tests have shown a reduction in blood clots, protein breakdown and free radicals. After eight weeks, skin texture was improved by 42 percent, puffiness around the eyes decreased by 31 percent, and dark circles under the eyes by 35 percent.

Peptides that give the lips more fullness:

•  Tripeptide-29 – The chain of three amino acids has been shown to increase fibroblast activity for the formation of collagen I by 400 percent. By plumping up the inside of the skin, thin lips and wrinkles are evened out.

 Peptides that make stretch marks appear less visible:

• Palmitoyl oligopeptide and palmitoyl tetrapeptide-7 – The combination of two peptides has a preventive effect against and reducing stretch marks by slowing down the degradation of ECM and at the same time promoting its regeneration. Studies show the increase in the formation of collagen I and fibronectin. After two months, stretch marks were less visible and the skin was smoother in places.

Bioactive peptides that moisturize:

Peptides that improve hydration:

Water is indispensable for the proper functions of the skin, especially for the proper barrier function. Water is constantly exchanged between the uppermost skin layers, the underlying epidermal layers and the environment. The aquaporins (AQP) play a special role as membrane proteins in the transport of water through the skin layers.

• Acetyl hexapeptide-37 – The skin hydration peptide supports the regulated flow of water from the basal cell layer of the epidermis to the layers of the skin surface by helping aquaporin 3 (AQP3) to work. AQP3 is the most abundant aquaporin in the epidermis. It enables transepidermal permeability, increases water content in the skin surface and strengthens barrier function. In tests, acetyl hexapeptide-37 increased skin hydration by 131 percent and collagen I formation by 61 percent.

Bioactive peptides that protect:

Peptides that prevent glycation and collagen cross-linking:

• Azeloyl tetrapeptide-23 – The rejuvenating aminopeptide reduces advanced glycation end products (AGEs). It prevents lipid peroxidation in the skin, reduces the formation of Reactive Oxygen Species (ROS) and protects cell membranes from attack by aggressive oxygen molecules. Studies confirmed a visible reduction of wrinkles and improved elasticity.

Peptides that soothe irritated and sensitive skin:

• Palmitoyl tripeptide-8 – The multifunctional neuropeptide supports skin homeostasis and helps alleviate irritation resulting from UV radiation, immune reactions, stress responses and mechanical influences. In tests, the neuropeptide reduced inflammatory cytokines by up to 64 percent, vasodilation by up to 51 percent and edema by up to 60 percent. In a post-shave relief test, 90 percent of participants said their skin felt more comfortable; 83 said irritation was relieved; 81 percent said razor burn calmed.

Peptides that rebalance stressed skin and restore the skin’s defenses:

• Acetyl tetrapeptide-22 – It increases the level of heat shock protein (HSP70) in the skin and thus strengthens the protective shield. The increase in this protein increases stress tolerance and thus prevents damage from further exposure to stress.

Bioactive peptides with special application:

Peptides that make the hair or eyelashes fuller:

• Myristoyl Pentapeptide-17 – It stimulates keratin and, when used with Myristoyl Hexapeptide-16, can lengthen lashes by 25 percent.
• Myristoyl hexapeptide-16 – It stimulates keratin and, when used with Myristoyl pentapeptide-17, can lengthen eyelashes by 25 percent.

Peptides as alternatives to hydroquinone for irritation-free lightening of the skin:

•  Oligopeptide-68 – The complex compound of TGF-ß agonist peptide inhibits microphtalmia-associated transcription factor (MITF). MITF is an important transcriptional regulator of melanogenesis enzymes, tyrosinase, TRP-1 and TRP-2. This peptide causes significant lightening of the skin; its activity is superior to that of arbutin and vitamin C.

Bioactive Peptides are ideally suited for the production of your cosmetics. Together with Cosmacon you will develop your product, so that it will certainly be a successful start to building your own brand.

Peptides in the future

Anti-aging skin care has seen many active ingredients come and go. However, bioactive peptides are more than a short-lived trend. Their applications are continually evolving and gaining in importance. We will be introduced to many new peptide products in the future. They are at their best when they are used in powerful formulations with sound anti-aging knowledge. Such products bring the best results, without irritation, without side effects, offering real alternatives. We are happy to develop high-quality and sophisticated formulations with bioactive peptides for you, feel free to contact us.

Sources:

Usage of Synthetic Peptides in Cosmetics for Sensitive Skin; Resende DISP, Ferreira MS, Sousa-Lobo JM, Sousa E, Almeida IF.Pharmaceuticals (Basel). 2021 Jul 21;14(8):702.

Beneficial Effects of Soybean-Derived Bioactive Peptides; Kim IS, Yang WS, Kim CH.Int J Mol Sci. 2021 Aug 9;22(16):8570.

Plant and Microalgae Derived Peptides Are Advantageously Employed as Bioactive Compounds in Cosmetics; Apone F, Barbulova A, Colucci MG.Front Plant Sci. 2019 Jun 12;10:756.

Anti-Wrinkle Benefits of Peptides Complex Stimulating Skin Basement Membrane Proteins Expression.; Jeong S, Yoon S, Kim S, Jung J, Kor M, Shin K, Lim C, Han HS, Lee H, Park KY, Kim J, Chung HJ, Kim HJ.Int J Mol Sci. 2019 Dec 20;21(1):73.