Improvement in Wrinkles by 2-Aza-8-oxohypoxanthine (AOH)


Skin aging, often characterized by the appearance of wrinkles, is a significant concern. One factor contributing to wrinkle formation is the decrease in stratum corneum water content, which is associated with compromised skin barrier function. Maintaining adequate hydration and a healthy skin barrier is crucial for skin health and appearance. Researchers have explored various compounds for their potential cosmetic efficacy in addressing these issues. This study focuses on 2-aza-8-oxohypoxanthine (AOH), one of the “fairy chemicals” identified in fungal fairy rings. Previous research has indicated that AOH possesses potential as a functional cosmetic ingredient, demonstrating a cytostatic effect on normal human epidermal keratinocytes (NHEKs) and upregulating genes involved in skin barrier function. Clinical trials have further substantiated its effectiveness in enhancing skin barrier function by increasing stratum corneum water content and reducing trans-epidermal water loss (TEWL), and it has also shown a skin lightening effect. Given the known link between decreased stratum corneum water content and wrinkle formation, the potency of AOH in wrinkle improvement was suggested. This clinical study was therefore conducted to evaluate the cosmetic efficacy of AOH in improving wrinkles.

Methods
A 12-week, double-blind, split-face, left-right randomized clinical trial was conducted involving 23 women (mean age 44 ± 8 years) who were concerned about dry skin and wrinkles. Participants applied either a 0.01% or 0.05% AOH lotion to each half of their face twice daily. Skin assessments were performed at baseline and at 4, 8, and 12 weeks, including measurement of stratum corneum water content using a Corneometer and wrinkle evaluation through image analysis of replicas from the crow’s feet area.

Key Findings

  • Application of AOH lotion enhanced stratum corneum water content.
  • The 0.05% AOH lotion group showed a statistically significant increase in stratum corneum water content at 8 weeks (p = 0.014) and 12 weeks (p = 0.004) compared to baseline.
  • The 0.05% AOH lotion group had a statistically significant greater increase in stratum corneum water content at 4 weeks (p = 0.025), 8 weeks (p = 0.002), and 12 weeks (p = 0.012) compared to the 0.01% AOH lotion group, demonstrating a concentration-dependent effect.
  • The 0.01% AOH lotion reduced the wrinkle area percentage at 8 weeks (p = 0.015) and 12 weeks (p = 0.043).
  • The 0.05% AOH lotion significantly reduced the wrinkle area percentage at 12 weeks (p = 0.014).
  • The 0.01% AOH application site showed a significant reduction in maximum wrinkle depth at 12 weeks (p = 0.042).
  • Maximum wrinkle depth at the 0.05% AOH application site was significantly reduced at 4 weeks (p = 0.002), 8 weeks (p < 0.001), and 12 weeks (p < 0.001).
  • Between-group comparisons indicated a statistically significant greater reduction in maximum wrinkle depth in the 0.05% AOH lotion group compared to the 0.01% group at 4, 8, and 12 weeks, demonstrating a concentration-dependent effect.
  • The mean maximum wrinkle depth at the 0.05% AOH application site was significantly reduced at 12 weeks (p = 0.005).
  • Visual assessment of skin images showed improved wrinkles at the corners of the eyes in all participants at 12 weeks, with greater enhancement in areas where the 0.05% AOH lotion was applied.
  • Human patch tests and the clinical trial usability questionnaire indicated that both 0.01% and 0.05% AOH lotions were safe for use, with no serious skin reactions or adverse events reported.


This study represents the first report demonstrating the concentration-dependent effects of AOH on both increasing stratum corneum water content and wrinkle reduction. The findings show that AOH significantly improved wrinkle parameters, including wrinkle area percentage, maximum wrinkle depth, and mean maximum wrinkle depth, alongside increased stratum corneum water content, with the 0.05% concentration generally yielding more pronounced results earlier and over the study period compared to the 0.01% concentration. The proposed mechanisms for AOH’s efficacy include the stimulation of hyaluronic acid production and the improvement of skin barrier function through the upregulation of relevant genes and potentially effects on tight junctions. Given the confirmed safety profile and demonstrated efficacy in improving skin barrier function, skin lightness, and now wrinkles, AOH is concluded to be a safe cosmetic ingredient with significant potential for reducing the appearance of fine lines and wrinkles, particularly those caused by dryness. This research supports the continued development and application of AOH in cosmetic formulations targeting skin hydration and wrinkle reduction, building upon its foundation as a multifaceted functional ingredient.

Link to the study: https://www.mdpi.com/2079-9284/12/3/114