α-ionone promotes keratinocyte functions and accelerates epidermal barrier recovery

α-紫罗兰酮促进角质形成细胞功能并加速表皮屏障恢复

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作者:Dandan Yang #, Mengli Fu #, Qi Zhao, Yong Wang, Tan Li, Bei Feng, Echuan Li, Yoshihito Nishijima, Zhenliang Sun, Zhenlin Hu

Background

As a common fragrance ingredient, α-ionone is widely used in cosmetics, perfume, and hygiene products. Nevertheless, little information is available for its biological activities on the skin. In this study, we investigated the effect of α-ionone on keratinocyte functions associated with skin barrier repair and further evaluated its skin barrier recovery capacity to explore its therapeutic potential for the treatment of skin barrier disruption.

Conclusions

These results demonstrated the role of α-ionone in the improvement of keratinocyte functions and the epidermal barrier recovery. These findings suggest possible therapeutic application of α-ionone in the treatment of skin barrier disruption.

Methods

The effect of α-ionone on the keratinocyte functions including cell proliferation, migration, and production of hyaluronic acid (HA) and human β-defensin-2 (HBD-2) were examined in vitro using human immortalized keratinocytes (HaCaT cells) as experimental model. The barrier recovery effects of topical hydrogels containing 0.1% or 1% α-ionone were tested on the volar forearm of 31 healthy volunteers by measuring transepidermal water loss (TEWL) and stratum corneum (SC) hydration following barrier disruption induced by repeated tape-stripping. The statistical significance was evaluated by one-way analysis of variance (ANOVA) followed by a Dunnett's post-hoc test.

Results

α-ionone promoted HaCaT cell proliferation (P<0.01) dose-dependently in the 10 to 50 µM range. Meanwhile, it also increased the intracellular cyclic adenosine monophosphate (cAMP) levels (P<0.05). Furthermore, HaCaT cells treated with α-ionone (10, 25, 50 µM) showed enhanced cell migration (P<0.05), up-regulated gene expression of hyaluronic acid synthases 2 (HAS2) (P<0.05), HAS3 (P<0.01), and HBD-2 (P<0.05), and enhanced production of HA (P<0.01) and HBD-2 (P<0.05) in the culture supernatant. These beneficial actions of α-ionone were abrogated by cAMP inhibitor, suggesting that its effects are cAMP-mediated in HaCaT cells. In vivo study showed that topical application of α-ionone-containing hydrogels accelerated the epidermal barrier recovery of human skin after barrier disruption by tape stripping. Treatment with hydrogel containing 1% α-ionone resulted in a significant increase of above 15% in the barrier recovery rate at day 7 post-treatment when compared to the vehicle control (P<0.01). Conclusions: These results demonstrated the role of α-ionone in the improvement of keratinocyte functions and the epidermal barrier recovery. These findings suggest possible therapeutic application of α-ionone in the treatment of skin barrier disruption.

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