Bin Fang

Skin yellowness is a hallmark of dull or unhealthy skin, particularly among Asians. Previous research has indicated a link between skin glycation and skin yellowness. However, the specific glycated chemicals contributing to yellowish skin appearance have not been identified yet. Using HPLC-PDA-HRMS coupled with native and artificially glycated human epidermal explant skin, we identified intensely yellow colored glycated chromophores “(1R, 8aR) and (1S, 8aR)-4-(2-furyl)-7-[(2-furyl)-methylidene]-2-hydroxy-2H,7H,8AH-pyrano-[2,3-B]-pyran-3-one” (abbreviated as AGEY) from human skin samples for the first time. The abundance of AGEY was strongly correlated with skin yellowness in the multiple skin explant tissues. We further confirmed the presence of AGEY in cultured human keratinocytes and 3D reconstructed human epidermal (RHE) models. Additionally, we demonstrated that a combination of four cosmetic compounds with anti-glycation properties can inhibit the formation of AGEY and reduce yellowness in the RHE models. In conclusion, we have identified specific advanced glycation end products with an intense yellow color, namely AGEY, in human skin tissues for the first time. The series of study results highlighted the significant contribution of AGEY to the yellow appearance of the skin. Furthermore, we have identified a potential cosmetic solution to mitigate AGEY formation, leading to a reduction in yellowness in the in vitro RHE models.

Sleep shortage is a major concern in modern life and induces various psycho-physical disorders, including skin problems. In cosmeceutics, females are aware that sleep deprivation worsens their facial skin tone. Here, we measured the effects of sleep deprivation on facial skin yellowness and examined yellow chromophores, such as bilirubin and carotenoids, in blood serum as potential causes of yellowness. Total sleep deprivation (0 h sleep overnight, N = 28) and repeated partial sleep deprivation (4 h sleep for 5 consecutive days, N = 10) induced significant increases in facial skin yellowness. The higher yellowness was sustained even after both sleep deprivation types stopped. However, circulating levels of yellow chromophores were unchanged in the total sleep deprivation study. Neither circulating interleukin-6 nor urinary biopyrrin levels were affected by total sleep deprivation, suggesting that apparent oxidative stress in the body was not detected in the present total deprivation protocol. Facial redness was affected by neither total nor repeated partial sleep deprivation. Therefore, blood circulation may play a limited role in elevated yellowness. In conclusion, facial skin yellowness was indeed increased by sleep deprivation in our clinical studies. Local in situ skin-derived factors, rather than systemic chromophore change, may contribute to the sleep deprivation-induced elevation of facial skin yellowness.

Sallow and/or dull skin appearance is greatly attributable to the yellow components of skin tone. Bilirubin is a yellow chromophore known to be made in the liver and/or spleen and is transported throughout the body via the blood stream. Recent publications suggest bilirubin may be synthesized in other cells/organs, including the skin. We found human keratinocytes express the transcripts involved in bilirubin biosynthesis. In parallel, we also found human keratinocytes could indeed synthesize bilirubin in monolayer keratinocytes and in a 3D human skin-equivalent model. The synthesized amount was substantial enough to contribute to skin yellowness. In addition, oxidative stress enhanced bilirubin production. Using UnaG, a protein that forms a fluorescent species upon binding to bilirubin, we also visualized the intracellular expression of bilirubin in keratinocytes. Finally, we screened a compound library and discovered that the sucrose laurate/dilaurate (SDL) combination significantly reduced bilirubin levels, as well as bilirubin-mediated yellowness. In conclusion, bilirubin is indeed synthesized in epidermal keratinocytes and can be upregulated by oxidative stress, which could contribute to chronic or transient yellow skin tone appearance. Application of SDL diminishes bilirubin generation and may be a potential solution to mitigate yellowish and/or dull skin appearance.