Skin dullness contributes to a fatigued and aged appearance, often exceeding one’s biological age. It is a common dermatological concern influenced by aging and poor lifestyle habits, regardless of ethnicity or age. This study aimed to examine advanced glycation end products (AGEs) and their receptor (receptor for AGEs [RAGE]) as contributing factors to skin dullness. AGEs themselves have a yellowish hue, contributing to “yellow dullness.” Additionally, AGE–RAGE signaling promotes melanin production in melanocytes and impairs keratinocyte differentiation as a result of inflammation. Therefore, regulating the AGE–RAGE interaction may help reduce skin dullness. Through screening various natural ingredients, we found that peony root extract (PRE) inhibits AGE formation and blocks AGE–RAGE binding. Furthermore, the presence of PRE leads to the suppression of AGE-induced melanin production in melanocytes and the restoration of impaired keratinocyte differentiation in glycated basement membrane components. In a human clinical study, topical application of a 1% PRE-containing lotion for 2 weeks significantly reduced melanin content, with a trend toward decreased AGE accumulation and visible spots on the cheeks. These findings support the potential of PRE as a multifunctional cosmetic ingredient that comprehensively addresses skin dullness by modulating the AGE–RAGE interaction.

Hyaluronic acid (HA) is an important component of the skin’s extracellular matrix, and its degradation leads to wrinkles. Hyaluronan-binding protein involved in hyaluronan depolymerization (HYBID) is the main factor responsible for HA degradation in dermis. This study aimed to identify natural plant materials that can effectively suppress HYBID expression and protect HA from degradation. Screening of various plant extracts was performed for the inhibition of histamine-induced mRNA expression of HYBID in normal human dermal fibroblasts (NHDF). The molecular size distribution of HA was evaluated by incubating fluorescein isothiocyanate (FITC)-labeled large HA (1200–1600 kDa) in NHDF for certain time followed by measuring different sizes of FITC-labeled HA in the cultured medium by HPLC. Among 380 plant extracts, we found that Artemisia capillaris flower extract (ACFE) was the most effective agent in both suppressing HYBID expression as well as protecting large HA from degradation. Subsequent mechanism elucidation studies showed that ACFE epigenetically regulates the expression of HYBID by modulating the expression of a specific miRNA, miR-486-5p, which is known to directly target and inhibit HYBID expression. Our active compound search identified 1-caffeoyl-3-hydroxybutane and 3-caffeoyl-1-hydroxybutane in ACFE as new compounds, which we named Kawarayomogin I and Kawarayomogin II, respectively. This is the first report to show that Artemisia capillaris with two novel active compounds inhibits HYBID expression as well as hyaluronic acid degradation, and therefore, could be used as possible agent for cosmeceutical potential.

GPNMB is a highly glycosylated type I transmembrane protein, which is known to be expressed in many cell types with multiple functions including |

Glycoprotein non-metastatic melanoma protein B (GPNMB) is a Type I transmembrane glycoprotein which has important roles in cancer and amyotrophic |