What beneficial effects do peptides have on the skin?

The peptides are short chains of amino acids that play a key role in the cellular communication and skin regeneration. They are particularly popular for preventing the skin ageing and reducing wrinkles. Indeed, certain specific peptides, known as messenger peptides or matrix peptides, directly stimulate the production of collagen, of elastin, glycosaminoglycans and fibronectin within the extracellular matrix. By strengthening this structure, the skin gains firmness and elasticity, and wrinkles and fine lines are reduced.

Among these peptides are palmitoyl tripeptide-1 (pal-GHK) and palmitoyl pentapeptide-4 (pal-KTTKS), which act as signalling messengers for fibroblasts, the cells responsible for the synthesis of collagen, elastin and glycosaminoglycans. Other peptides, such as palmitoyl tripeptide-3/5, mimic extracellular matrix proteins and contribute both to the stimulation of collagen synthesis and to the prevention of its degradation, thereby reinforcing the skin’s overall structure.

There are also peptides targeting muscle relaxation, known as neurotransmitter-inhibiting peptides, such as acetylhexapeptide-3 (Argireline) or pentapeptide-18, which act on the contraction of the muscles responsible for expression lines. By modulating the release of acetylcholine at nerve terminals, these peptides reduce the intensity of muscle contractions, resulting in a gradual smoothing of dynamic wrinkles, without the invasive effects of treatments such as the botox.

The efficacy of peptides in reducing wrinkles is not based solely on mechanistic hypotheses: several clinical studies have confirmed their visible effects on the skin. Among these, a recent study focused on tetrapeptide-68, a peptide derived from loricrin, a skin barrier protein. Conducted over 12 weeks in a double-blind design, the study included 25 participants who applied a cream containing 100 ppm of tetrapeptide-68 twice daily. Researchers monitored various physiological skin parameters measuring wrinkle roughness, depth and density. The results showed a significant reduction in all these parameters, with a progressive improvement from the fourth week and maximum effect at 12 weeks.

Antioxidant peptides represent a new generation of active ingredients capable of reinforcing the skin’s natural defences against free radicals. Some, such as carnosine, glutathione or anserine, occur naturally in the body or in certain foods, but the majority of antioxidant peptides used in cosmetics are derived from enzymatic hydrolysis or the fermentation of plant and animal proteins. These processes produce short chains of amino acids capable of neutralising free radicals, chelating heavy metals (such as iron and copper) and limit lipid peroxidation within cellular membranes.

The efficacy of antioxidant peptides is closely tied to their molecular structure, particularly their size and amino acid composition. Peptides rich in hydrophobic residues such as leucine, alanine or proline, or in aromatic amino acids like tryptophan, phenylalanine or histidine, exhibit an enhanced ability to donate electrons or hydrogen atoms to free radicals. Histidine, in particular, functions via its imidazole ring, which can participate in both electron and hydrogen transfer reactions. Peptides of low molecular weight (< 1 kDa) also demonstrate superior skin penetration and greater mobility in biological media, thereby optimising their antioxidant activity.

How do antioxidant peptides benefit the skin?

By neutralising free radicals and reinforcing enzymatic defence systems, antioxidant peptides act as a shield against oxidative stress. They prevent the peroxidation of membrane lipids, the fragmentation of collagen and the degradation of elastin, thus maintaining the firmness and elasticity of the skin. Their ability to stabilise pro-oxidant metals, such as iron or copper, also limits the formation of reactive hydroxyl radicals. In parallel, activation of the Nrf2–ARE pathway promotes the natural production of protective enzymes, such as superoxide dismutase, catalase and glutathione peroxidase, enhancing cellular resilience against UV rays and pollution.

Antioxidant peptides help maintain the skin’s smoothness and radiance and protect it against the signs of ageing.

Wound healing is a highly orchestrated process involving inflammation, cell migration, fibroblast proliferation and extracellular matrix reconstruction. Several peptides, notably the antimicrobial peptides clavanin A and LL-37, have demonstrated notable pro-regenerative activity on skin cells. In addition to their anti-infective role, these peptides exert an immunomodulatory action that balances pro- and anti-inflammatory responses, thereby favouring an environment conducive to tissue repair.

Studies on human fibroblasts have shown that these peptides stimulate cell proliferation and migration by activating the transcription of certain genes, such as KI67 (cell proliferation) and CXCR4 (receptor involved in cell migration). These mechanisms are accompanied by accelerated reconstruction of the dermal tissue, with an increased production of collagen, elastin and proteoglycans, necessary for the restoration of skin structure. Other peptides, such as hBD-2, hBD-3, Crotalus adamanteus toxin-II or PR-39, also enhance wound healing by stimulating the FGFR1/JAK2/STAT3 signalling pathway, known for promoting angiogenesis and fibroblast activation.

An experimental study conducted in a mouse model revealed the strong wound-healing potential of the RL-QN15 peptide. Mice with dorsal wounds received twice-daily topical applications of RL-QN15 at various concentrations, compared with a control group and a positive control (Kangfuxin, known for its healing properties). After just 7 days of treatment, the wounds treated with 50 nM RL-QN15 showed a near-complete regeneration (≈ 100%), significantly greater than that of the control group, whose healing reached only about 60%. The peptide’s efficacy proved dose-dependent, with activity comparable to Kangfuxin but at a concentration roughly five million times lower, emphasising its potency. Histological analyses confirmed a rapid, orderly reconstruction of the epidermis and dermis, accompanied by the formation of a finer granulation tissue, indicative of higher-quality healing and a reduced risk of fibrosis.

Adequate hydration is essential for maintaining the barrier function of the skin, which acts as a genuine protective interface between the body and the external environment. The hydrolipidic film, the intercellular lipids of the stratum corneum and the natural moisturising factors are key elements of this barrier. When well hydrated, the skin retains its suppleness, resilience and regenerative capacity. Conversely, skin dehydration disrupts the cellular cohesion of the stratum corneum, increases transepidermal water loss and promotes irritation and premature ageing.

Certain biomimetic peptides stand out for their hydrating properties. A 30-day clinical study assessed the moisturising effects of a hydrogel enriched with biomimetic peptides (SH-Oligopeptide-2, SH-Polypeptide-1, SH-Oligopeptide-1, SH-Polypeptide-42) on the skin of 20 women. The results showed a significant improvement in skin hydration from the first application, compared with untreated skin and a placebo (gel without peptides). These effects were accompanied by a significant enhancement of skin elasticity and radiance, confirming the multifunctional role of the peptides.

Peptides are also valued for their anti-inflammatory properties, particularly beneficial for sensitive skin, often prone to redness and discomfort. Among these, one can cite acetyl dipeptide-1 cetyl ester, which acts directly on the POMC (pro-opiomelanocortin) gene pathway, leading to the production of peptides, such as α-MSH, that contribute to the modulation of inflammation. Studies have also shown that it stimulates the expression of genes essential to barrier function, such as AQP3, filaggrin, caspase-14 and keratin-10, while decreasing the production of prostaglandin E2, a mediator of cutaneous hypersensitivity reactions. These combined effects enable the skin to better withstand aggressions.

Other peptides, such as palmitoyl tripeptide-8, have likewise demonstrated soothing effects. Palmitoyl tripeptide-8, inspired by α-MSH, inhibits the production of interleukin-8, a pro-inflammatory cytokine. A study involving 13 volunteers evaluated its soothing effect following skin irritation induced by a 0.5% solution of sodium lauryl sulfate (SDS), known to induce local inflammation and redness. After 24 hours’ contact with the SDS, participants applied a formulation containing 4 × 10⁻⁶ M palmitoyl tripeptide-8 or a placebo, three times a day, for two days. Thermographic measurements revealed that the SDS-induced rise in skin temperature was reduced by an average of 78% in the peptide-treated area, whereas no significant improvement was seen with the placebo. Video microscopy observations confirmed a visible reduction in redness and inflammation following the application of palmitoyl tripeptide-8, illustrating its soothing and anti-inflammatory power on irritated skin.

Thanks to their antibacterial and anti-inflammatory properties, certain peptides are considered promising allies in the fight against blemishes. Moreover, unlike conventional antibiotics, these molecules do not target a single mechanism in the bacteria involved in acne pathogenesis but directly disrupt its cell membrane, making the development of resistance more difficult. A recent study highlighted the potential of peptide P156, a derivative of phage lysine Prevotella intermedia (PlyPi01), to target the bacteria Cutibacterium acnes and Staphylococcus aureus, associated with the inflammatory flare-ups of acne.

Although these results are promising, caution is warranted in their interpretation. The observed antibacterial effects have been demonstrated only in vitro, under controlled laboratory conditions and have not yet been confirmed by clinical studies on human skin. Moreover, although these molecules effectively target the bacteria involved in acne, they exhibit neither keratolytic activity nor mattifying properties, two essential aspects in the comprehensive management of blemishes. Thus, antibacterial peptides will likely need to be combined with other actives to provide a full-spectrum action on the various mechanisms of acne.

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