Which other active ingredients can argireline be combined with?

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

In cosmetics, several forms of hyaluronic acid coexist: high molecular weights (> 1,000 kDa) remain on the skin’s surface and form a film that limits water loss, while low molecular weights (< 500 kDa) penetrate the stratum corneum and participate in regulating genes related to filaggrin and epidermal lipid synthesis, thereby helping strengthen the skin barrier. With age, hyaluronic acid production decreases, weakening tissue cohesion and deepening wrinkles. Topical application can partially offset this decline, especially when different molecular weights are combined.

This combination of effects makes hyaluronic acid a particularly relevant partner for argireline, as the former enhances skin hydration and tissue density, while the latter specifically targets the muscle contractions involved in expression lines.

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

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

Indeed, the retinoids act at a deep level, in the epidermis and dermis, stimulating collagen production and improving the quality of the extracellular matrix. The argireline, for its part, targets a different mechanism: modulating the release of neurotransmitters involved in muscle contraction, which helps to reduce expression lines. By combining these two modes of action, one could achieve a cosmetic formula that works on multiple levels to combat the signs of aging. This synergy is therefore promising, but remains hypothetical today and still needs to be confirmed by clinical studies.

The vitamin C, or ascorbic acid, is one of the most studied active ingredients in dermatology for its dual role as an antioxidant and a cofactor in collagen synthesis. It neutralizes free radicals generated during metabolism, as well as those induced by UV exposure and pollution, thereby limiting oxidative reactions that accelerate skin aging. Biologically, vitamin C enhances the activity of prolyl- and lysyl-hydroxylase enzymes, essential for the stabilization and maturation of collagen fibers, while inhibiting melanin production via an 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 sodium ascorbyl phosphate and ascorbyl tetraisopalmitate.

Combining vitamin C with argireline could be promising for preventing photoaging 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 dermal scaffold, where it forms a dense network of fibers ensuring its mechanical strength, firmness, and flexibility. When applied topically, its action is slightly different. In its native form, the collagen primarily serves as a moisturizer, due to its hydrophilic structure. Some in vitro studies have also shown that collagen peptides – when they are small enough to cross the skin barrier – possess antioxidant properties: they neutralize free radicals, thereby protecting cellular components from oxidative stress. Finally, collagen peptides appear capable of stimulating fibroblast activity and the production of endogenous collagen. Several clinical studies have even demonstrated that daily application of collagen can have a firming effect.

Combining argireline with collagen could therefore provide a complementary strategy against the signs of aging.

Indeed, on one hand, argireline would limit the muscle contractions responsible for expression wrinkles, while collagen would hydrate the skin and, in peptide form, reinforce its structure and antioxidant defense. This theoretical synergy is all the more interesting because 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 type I collagen content compared to the control group. However, this is a preliminary finding, still far from clinical demonstration in humans. Based on current knowledge, this association remains promising but needs confirmation through more in-depth studies.

Today there is a wide variety of peptides used in cosmetics, many of which target skin aging, but through different mechanisms, which makes their combination 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 strengthening dermal structure and improving skin firmness. Others, such as carnosine, possess antioxidant properties and protect skin cells from oxidative stress. In addition, copper peptides, such as GHK-Cu, have strong reparative properties with anti-inflammatory activity and could also be beneficially combined with argireline. Finally, several peptides biomimetic peptides enhance skin hydration.

In practice, argireline can be combined with other peptides to deliver neuromodulatory activity alongside benefits for 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).