Which other active ingredients can argireline be combined with?

The hyaluronic acid is a glycosaminoglycan naturally present in the epidermis and dermis, where it plays an essential role in maintaining skin hydration and organising the extracellular matrix. Its linear structure, composed of repeating units of glucuronic acid and N-acetylglucosamine, enables it to bind up to 1,000 times its weight in water, which explains its function as a humectant major.

In cosmetics, several forms of hyaluronic acid coexist: high molecular weight fractions (> 1,000 kDa) remain on the skin’s surface, forming a film that limits water loss, while low molecular weight fractions (< 500 kDa) penetrate the stratum corneum and modulate genes involved in filaggrin and epidermal lipid synthesis, thus contributing to the reinforcement of the skin barrier. With age, hyaluronic acid production declines, compromising tissue cohesion and accentuating wrinkles. Topical application can partly offset this decline, especially when different molecular weights are combined.

This combination of effects makes hyaluronic acid a particularly relevant partner for argireline, since one acts on skin hydration and tissue density, while the other targets the muscular contractions involved in expression lines.

The retinoids encompass all vitamin A derivatives, whose mode of action relies primarily on their ability to bind to the nuclear receptors RAR and RXR, modulating the expression of genes involved in keratinocyte proliferation, cell differentiation and extracellular matrix synthesis. They are widely used in dermatology and cosmetics to reduce wrinkles, even out skin tone and refine skin texture. The retinol is the most commonly used form in cosmetics. After application, it undergoes two successive oxidations to convert into retinoic acid, the biologically active form. Other variants exist: retinaldehyde, which is converted more rapidly into retinoic acid; retinol esters, which are better tolerated but less potent; and tretinoin, available only on prescription.

Combining retinoids with argireline holds considerable theoretical interest, although no study has yet directly evaluated this combination.

Indeed, the retinoids act deeply at the epidermal and dermal levels, stimulating collagen production and improving the quality of the extracellular matrix. The argireline, meanwhile, targets a different mechanism: modulating the release of neurotransmitters involved in muscle contraction, which helps reduce expression lines. By combining these two modes of action, one could develop a cosmetic formulation that works on multiple levels to combat the signs of ageing. This synergy therefore appears promising, but remains hypothetical today and must still be confirmed by clinical studies.

The vitamin C, or ascorbic acid, is one of the most extensively studied actives in dermatology for its dual role as an antioxidant and as a cofactor in collagen synthesis. It neutralises free radicals generated during metabolism, as well as those from UV exposure or pollution, thereby limiting oxidative reactions that accelerate skin ageing. On a biological level, the vitamin C stimulates the activity of prolyl- and lysyl-hydroxylase enzymes, essential for the stabilisation and maturation of collagen fibres, while also inhibiting melanin production via action on tyrosinase. In cosmetics, different forms of vitamin C coexist: pure L-ascorbic acid, highly effective but unstable, and more stable derivatives, such as the sodium ascorbyl phosphate and ascorbyl tetraisopalmitate.

Combining vitamin C with argireline may offer benefits in preventing photoageing and the development of expression lines. However, to date, no study has specifically evaluated this combination.

Collagen plays a fundamental role in the architecture of the skin : it constitutes the framework of the dermis, where it forms a dense network of fibres providing mechanical strength, firmness and suppleness. When applied topically, its action is slightly different. In its native form, the collagen primarily has a hydrating function, owing to its hydrophilic structure. Some in vitro studies have also shown that the peptides of collagen – when sufficiently small to penetrate the skin barrier – possess antioxidant properties: they neutralise free radicals, thereby protecting cellular components from oxidative stress. Finally, collagen peptides appear capable of stimulating fibroblast activity and endogenous collagen production. Several clinical studies have moreover shown that daily application of collagen can have a firming effect.

Combining argireline with collagen could therefore offer a complementary strategy against the signs of ageing.

Indeed, on one hand, argireline would limit the muscular contractions responsible for expression lines, while collagen would hydrate the skin and, in peptide form, strengthen its structure and antioxidant defence. This theoretical synergy is all the more intriguing as preliminary data suggest a potential link between argireline and the synthesis of collagen : skin biopsies from mice treated with a 10% argireline solution showed a higher content of type I collagen compared with the control group. However, this is a preliminary finding, still far from clinical demonstration in humans. As things stand, this combination remains promising but requires confirmation by more in-depth studies.

Today, there is a wide diversity of peptides used in cosmetics, many of which target skin ageing, but through different mechanisms, making their combination particularly interesting. Some, such as palmitoyl tripeptide-1 (Pal-GHK) or palmitoyl pentapeptide-4 (Pal-KTTKS), act directly on fibroblast activity: they stimulate the production of collagen, elastin and glycosaminoglycans, thereby reinforcing the dermal structure and improving skin firmness. Others, such as carnosine, possess antioxidant properties and protect skin cells from oxidative stress. Added to these are copper peptides, such as GHK-Cu, which have strong reparative power alongside anti-inflammatory activity, and which could also be relevant to combine with argireline. Finally, several peptides biomimetic ones enhance skin hydration.

In practice, argireline can be combined with other peptides to deliver a neuromodulatory effect alongside improvements in skin suppleness, hydration or antioxidant protection.

• WANG Y. & al. The anti-wrinkle efficacy of argireline, a synthetic hexapeptide, in Chinese subjects. American Journal of Clinical Dermatology (2013).

• BUDZISZ E. & al. Retinoids: Active molecules influencing skin structure formation in cosmetic and dermatological treatments. Advances in Dermatology and Allergology (2019).

• FAHS F. & al. A review of topical vitamin C derivatives and their efficacy. Journal of Cosmetic Dermatology (2021).

• AHMED M. A. & al. A review of the cosmetic use and potentially therapeutic importance of hyaluronic acid. Journal of Applied Pharmaceutical Science (2022).

• YI T.-H. Sustainable dynamic wrinkle efficacy: Non-invasive peptides as the future of botox alternatives. Cosmetics (2024).