Injected botulinum neurotoxins (BoNT) reduce dynamic wrinkles by cleaving SNARE proteins at the neuromuscular junction; however, their large size mostly limits their use to injectable procedures. Certain polyphenols, including myricetin, have been shown in neuronal systems to reduce acetylcholine (ACh)-induced muscle contraction via inhibition of SNARE complex zippering, suggesting potential for topical use as modulators of skin cholinergic activity. This study aimed to identify a natural extract blend similarly capable of attenuating ACh release followed by characterization of the activity of this extract on human skin explants, alongside reference molecules BoNT/A, α-bungarotoxin, and myricetin. The natural extract blend (“Blend 1”) inhibited vesicle fusion and attenuated norepinephrine release in a cell culture system, inhibited muscle cell contraction within nerve/muscle co-culture, and attenuated ACh release consistent with myricetin and reference neurotoxins within human skin explants. Bulk transcriptomics of treated ex vivo skin explants revealed that BoNT/A, myricetin and Blend 1 all shared a similar downregulated inflammatory and anti-viral gene profile separate from α-bungarotoxin, but that myricetin and Blend 1 shared a large degree of overlap for upregulated genes associated with skin homeostasis and repair that was not observed for either toxin. These data support Blend 1 as a candidate for topical cosmetic use through modulation of BoNT/A-like cholinergic pathways, alongside activation of additional pathways associated with skin homeostasis and repair.

Skin aging is a complex and multifactorial phenomenon. While retinoids and vitamin C are considered gold standards in anti-aging, their side effects can be problematic. In this context, we have developed a novel combination of active ingredients: maitake, a peptide complex, and rhamnose, designed to improve the signs of aging by primarily targeting collagen. This study aimed to compare, in vitro, the effects of our new combination with those of retinol, retinoic acid, and vitamin C.The different treatments were evaluated in a human skin model reconstituted in vitro from aged cells by measuring epidermal thickness and the expression of key biomarkers in the epidermis, the dermo-epidermal junction (DEJ), and the dermis. The efficacy of each treatment was then compared using a scoring system.Our combination of active ingredients significantly reversed the aged phenotype by restoring epidermal thickness and stimulating hyaluronic acid production as well as the expression of key proteins such as DSG-1 and Collagens I, IV, V, VI, and VI. This mix demonstrated overall performance comparable to that of retinol, but superior to that of retinoic acid and vitamin C.These results show that this new combination is a promising anti-aging solution, offering comprehensive action and potentially improved tolerability. In vivo clinical studies will be necessary to confirm these promising in vitro results.Graphical This study evaluates and compares the anti-aging efficacy of [MAI: M3K: RHA] mix, Retinol, Retinoic acid and Ascorbic acid in a reconstructed human aged skin by measuring their capacity to reverse the aged phenotype.

Injected botulinum neurotoxins (BoNT) reduce dynamic wrinkles by cleaving SNARE proteins at the neuromuscular junction; however, their large size mostly limits their use to injectable procedures. Certain polyphenols, including myricetin, have been shown in neuronal systems to reduce acetylcholine (ACh)-induced muscle contraction via inhibition of SNARE complex zippering, suggesting potential for topical use as modulators of skin cholinergic activity. This study aimed to identify a natural extract blend similarly capable of reducing ACh levels, followed by characterization of the activity of this extract on human skin explants, alongside reference molecules BoNT/A, α-bungarotoxin, and myricetin. The natural extract blend (“Blend 1”) inhibited vesicle fusion and attenuated norepinephrine release in a cell culture system, inhibited muscle cell contraction within nerve/muscle co-culture, and reduced ACh levels consistent with myricetin and reference neurotoxins within human skin explants. Bulk transcriptomics of treated ex vivo skin explants revealed that BoNT/A, myricetin, and Blend 1 all shared a similar downregulated inflammatory and antiviral gene profile separate from α-bungarotoxin, but that myricetin and Blend 1 shared a large degree of overlap for upregulated genes associated with skin homeostasis and repair that was not observed for either toxin. These data support Blend 1 as a candidate for topical cosmetic use through modulation of BoNT/A-like cholinergic pathways, alongside activation of additional pathways associated with skin homeostasis and repair.