Antiwrinkle efficacy of 1‐ethyl‐β‐N‐acetylglucosaminide, an inducer of epidermal hyaluronan production

Abstract

Background Hyaluronan (HA) has a unique hydration capacity that contributes to firmness and bounciness of the skin. Epidermal HA declines with skin aging, which may lead to clinical signs of aging including skin wrinkles and loss of hydration and elasticity. Recently, we developed a new cosmetic agent 1‐ethyl‐β‐N‐acetylglucosaminide (β‐NAG2), which enhances HA production in cultured human keratinocytes. The aim of this study was to explore antiaging potential of β‐NAG2 in reconstructed human epidermal models and human clinical trial. Materials and methods The amount of HA in β‐NAG2‐treated epidermal models by topical application was analyzed by enzyme‐linked immunosorbent assay (ELISA)‐like assay. A randomized, double‐blind and placebo‐controlled study was conducted in Japanese females (n = 33) by topically treating each side of the face with a lotion formulated with β‐NAG2 or placebo for 8 weeks. Results Topically applied β‐NAG2 dose dependently increased HA production in epidermal models. Treatment with β‐NAG2‐formulated lotion significantly improved skin hydration and elasticity and reduced skin wrinkling in crow's foot areas when compared to the placebo formulation. Conclusion Topically applied β‐NAG2 promoted epidermal HA production in vitro and showed antiwrinkle activity in vivo accompanying the improvement in skin hydration and elasticity. Our study provides a novel strategy for antiwrinkle care through β‐NAG2‐induced epidermal HA production.

A Connecting Link between Hyaluronan Synthase 3-Mediated Hyaluronan Production and Epidermal Function

“…Therefore, it is tempting to speculate that HAS3-mediated HA production, rather than the extracellular level of epidermal HA, may be linked to epidermal organization and function, including keratinocyte proliferation and differentiation, at least in the developing epidermis in reconstructed epidermal equivalents. This notion is supported by our previous findings that 1-ethyl-β-N-acetylglucosaminide, an inducer of HAS3-mediated HA production [21], caused epidermal thickening by accelerating keratinocyte proliferation and differentiation [22,23]. However, since small HA oligosaccharides, which are known to induce keratinocyte proliferation and differentiation [36,37], could not be measured with the HA ELISA assay, we cannot exclude the possibility that changes in HA size by St-HAase treatment may influence epidermal organization and architecture.…”

“…Conversely, the reduction in epidermal HA by the HA synthesis inhibitor 4-methylumbelliferone (4MU) in organotypic cultures of rat keratinocytes or by a deficiency in the cell surface HA receptor CD44 in mice led to decreased keratinocyte proliferation and differentiation, respectively [ 19 , 20 ]. Furthermore, we recently reported that enhanced epidermal HA production mediated by 1-ethyl-β- N -acetylglucosaminide, a new inducer of epidermal HA production [ 21 , 22 ], resulted in epidermal thickening by accelerating keratinocyte proliferation and differentiation in reconstructed human skin equivalents [ 23 ]. Therefore, epidermal HA is generally considered to boost epidermal proliferation and differentiation.…”