A Potential Role of Keratinocyte-Derived Bilirubin in Human Skin Yellowness and Its Amelioration by Sucrose Laurate/Dilaurate

Abstract

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.

Sleep Deprivation Increases Facial Skin Yellowness

“…As circulating blood chromophores such as bilirubin and carotenoids may influence the yellowness of facial skin [ 16 , 22 , 23 ], we measured their blood levels. However, no significant alteration was observed in their blood levels during pre-deprivation, total sleep deprivation, and post-deprivation phases ( Figure 5 ).…”

“…Skin tone is known to be influenced by various chromophores, the most representative of which are melanin, hemoglobin, bilirubin, and carotenoids [ 16 , 22 , 23 , 29 , 30 , 31 ]. Among these chromophores, melanin and hemoglobin have the largest influence on overall skin tone [ 31 ].…”

“…However, few studies examining the effects of sleep deprivation on facial skin dullness have been carried out. Sallow and/or dull skin appearance is greatly attributable to the yellow components of skin tone [ 16 ]. Dullness and yellowness of the skin have been reported to be major concerns of Asian women [ 17 ].…”

Transcriptomic Analysis of Human Keratinocytes Treated with Galactomyces Ferment Filtrate, a Beneficial Cosmetic Ingredient

“…The keratinocyte cell line tKC (tert keratinocytes) was a kind gift from Dr. Jerry W. Shay (University of Texas Southwestern, Dallas, TX, USA) [ 21 , 22 ]. tKC cells were plated at a density of 100,000 cells/well into 12-well plates (Corning BioCoat, REF 354500; Corning Inc., Corning, NY, USA).…”

“…We used three different lots of GFF in this study. Transcriptomic analysis was performed as reported previously [ 22 ]. Briefly, samples were collected in RNAlater® buffer, flash-frozen, and stored at −80 °C prior to RNA extraction.…”