Bioactive peptides have gained significant attention in the cosmetic industry due to their potential in enhancing skin health and beauty. These small protein fragments exhibit various biological activities, such as antioxidant, anti-aging, anti-inflammatory, and antimicrobial activities, making them ideal ingredients for cosmetic formulations. These bioactive peptides are classified into four categories: signal, carrier, neurotransmitter-inhibitory, and enzyme-inhibitory peptides. This review provides insight into applying bioactive peptides in cosmetics and their mechanisms of action (e.g., downregulating pro-inflammatory cytokines, radical scavenging, inhibiting collagen, tyrosinase, and elastase synthesis). The abundant natural origins (e.g., animals, plants, and marine sources) have been identified as primary sources for extractions of cosmetic peptides through various techniques (e.g., enzymatic hydrolysis, ultrafiltration, fermentation, and high-performance liquid chromatography). Furthermore, the safety and regulatory aspects of using peptides in cosmetics are examined, including potential allergic reactions and regulatory guidelines. Finally, the challenges of peptides in cosmetics are discussed, emphasizing the need for further research to fully harness their potential in enhancing skin health. Overall, this review provides a comprehensive understanding of the application of peptides in cosmetics, shedding light on their transformative role in developing innovative and effective skincare products.
There is no denying that cosmetics have become an essential part of our daily routine, especially among women, and the cosmetic market, especially for natural ingredient-based products, is growing rapidly with a great demand for appearance improvement from consumers. Particularly, the development of novel cosmetic formulations based on bioactive compounds (e.g., antioxidants, proteins, peptides, and growth factors) with therapeutic and protective functions that can provide outstanding effects on human skin such as skin whitening, skin moisturizing, and skin rejuvenation, has quickly expanded.
Peptides are short chains of two to fifty amino acids linked together by peptide bonds. Amino acids are the building blocks of proteins, and when they are joined in a chain, they form a peptide. Peptides are smaller than proteins and typically composed of up to 50 amino acids, although specific thresholds can vary. Among the prominent bioactive compounds, peptides have attracted the attention of scientists due to their ideal functionalities, especially as regulating/signaling molecules of homeostasis, stress, immunity, defense, growth, and reproduction, and their other strengths such as high safety, hypo-allergenicity, and their cost-effective production. Derived from various natural sources such as plants, animals, and microorganisms, these peptides have demonstrated diverse physiological effects, including antioxidant, anti-aging, moisturizing, collagen-stimulating, and wound-healing properties, which have been confirmed through several in vitro/in vivo pieces of evidence as well as clinical trial outcomes. For instance, palmitoyl pentapeptide-3 was one of the first synthetic bioactive peptides used to stimulate collagen synthesis for anti-aging and wound healing treatments. The copper Gly–His–Lys (Cu-GHK) was developed and incorporated into cosmetic products to heal skin, promote collagen synthesis, and repair DNA damage. Acetyl hexapeptide-3 (Argireline®) is another popular commercialized peptide with potential anti-wrinkle and moisturizing properties.
Despite the growing scientific evidence supporting their potential application in cosmetics, there are only a handful of literature reports describing findings regarding promising applications. For instance, Ferreira et al. (2020) described the utilization of peptides for anti-aging treatment, but did not include treatment of all skin conditions. Mazurkiewicz-Pisarek et al. (2023) reported applying antimicrobial peptides only for pharmaceutical, biomedical, and cosmeceutical applications. Therefore, documenting the latest research and advancements in a review is necessary to provide comprehensive knowledge that can inspire further innovation in the formulation of peptide-based cosmetic products. In addition, there is a growing consumer demand for safe and effective cosmetic products with ingredients of natural or biological origin. Educating consumers about the potential of bioactive peptides through a well-written paper can help them make informed choices when selecting cosmetic products. It can be seen that understanding the potential of bioactive peptides in cosmetics can have broader implications beyond the cosmetic industry. Therefore, this review aims to explore the vast potential of bioactive peptides for cosmetic applications, shedding light on their intracellular mechanisms of action, their classifications, and their natural origins. It will delve into their multifaceted roles in skin health and beauty, addressing the underlying scientific principles and presenting relevant empirical evidence from both in vitro and in vivo studies. Moreover, it will discuss the safety assessment and challenges associated with using bioactive peptides in cosmetic formulations.
It has been demonstrated that bioactive peptides can exert their biological as well as cosmetic functions in different ways; thus, they are commonly classified into four categories according to their most outstanding features which includes signal peptides, carrier peptides, neurotransmitter-inhibitory peptides, and enzyme-inhibitory peptides.
Signal peptides are active compounds that can prevent aging by stimulating skin fibroblasts, resulting in increased biological responses such as collagen, elastin, fibronectin, glycosaminoglycan, and proteoglycan production. They may act as growth factors to activate protein kinase C which is mainly responsible for cell growth and migration.
One of the first cosmetic signal peptides is the palmitoyl peptide (Pal–Lys–Thr–Thr–Lys–Ser), which shows collagen modulating capabilities for anti-wrinkle and wound healing. It is a sub-fragment of the carboxyl terminal pro-peptide of type I collagen that can dramatically enhance extracellular matrix production in fibroblasts, thereby effectively stimulating collagen (I, II, and III) and fibronectin production. Aruan et al. (2023) conducted a double-blind, split-face, placebo-controlled, and left-right randomized trial with 21 female subjects to assess the clinical efficacy of anti-wrinkle cream containing the peptide. The result showed that in the course of a 12-week clinical trial, topical application of 3 ppm palmitoyl peptide reduced facial wrinkles/fine lines. Another signal peptide that stimulates collagen synthesis is palmitoyl tripeptide-5 (palmitoyl–Lys–Val–Lys), which can mimic the effect of thrombospondin-1, a naturally occurring molecule that causes the sequence Lys–Arg–Phe–Lys to bind to the inactive transforming growth factor-β (TGF-β), consequently, promoting the release of the active form of TGF-β. Thereafter, activated TGF-β causes a constant increase in the amount of type I and III collagen produced in dermal fibroblasts. A number of studies have demonstrated that palmitoyl tripeptide-3/5 enhances collagen synthesis and reduces collagen breakdown by interfering with MMP-1 and MMP-3 collagen degradation, leading thereby to improvements in aging signals. For example, a controlled trial was conducted on 60 Chinese volunteers treated with palmitoyl pentapeptide-5 (2.5%) cream compared with a placebo cream (for 84 days and applied twice daily). It was confirmed that palmitoyl tripeptide-5 significantly reduced skin roughness, exhibiting a greater anti-wrinkle efficacy than the placebo or pal-KTTKS-containing creams. Other commercialized signal peptides modulating collagen synthesis are described in terms of their anti-aging properties and mechanisms.
Regarding the enhancement of elastin contents in the skin, several signal peptides (e.g., dipeptide-2/valy tryptophan, Val–Gly–Val–Ala–Pro–Gly, and palmitoyl oligopeptide) have been developed to stimulate elastin synthesis, leading to improved skin aging signals. For instance, hexapeptide Val–Gly–Val–Ala–Pro–Gly and its modified sequence palmitoyl hexapeptide-12 are highly specific to elastin molecules that stimulate collagen and elastin fibroblasts, as well as develop glycosaminoglycans and fibronectin. The intracellular mechanism refers to the way in which they can reduce the production of proinflammatory mediators (e.g., IL-1, IL-6, and IL-8) and ultimately slow down the skin matrix’s degradation. Another signal peptide, palmitoyl oligopeptide, which contains such an elastin fragment, has been incorporated into cosmetic products to promote the proliferation of collagen, elastin, and hyaluronic acid, a role which suggests “reconstruction of the dermis” and “chemotaxis for restructuring and repair” properties. Hahn et al. (2016) produced an anti-aging facial cream containing 1% palmitoyl oligopeptide, Silybum marianum seed oil, vitamin E, and other functional ingredients to combat facial wrinkles. After 4 weeks of application, the volunteers’ crow’s feet wrinkles were reduced by 14.07% compared to pre-application, and the skin elasticity was observed to have increased by 8.79%. They were able to confirm, therefore, that a blend of palmitoyl oligopeptide and other cosmetics has a beneficial effect on facial wrinkles, elasticity, and skin tone.
Carrier peptides have been designed to deliver essential wound healing cofactors for enzymatic processing and wound repair.
