Targeting Circadian Rhythm for the Regulation of Skin Collagen Metabolism

Collagen is essential for maintaining skin structure and function, and the circadian rhythm is known to regulate a wide range of physiological processes.

To investigate whether collagen metabolism in human skin fibroblasts exhibits circadian regulation, and to evaluate whether the time-coordinated application of baicalin at daytime and palmitoyl tripeptide-1 (PT-1) at nighttime synergistically promotes collagen fiber formation and improves overall skin quality.

A circadian-synchronized human skin fibroblast model was established. The expression of collagen metabolism-related genes was analyzed using qPCR and immunofluorescence. Subsequently, an 8-week topical application study was conducted in mice using a regimen of daytime baicalin and nighttime PT-1. Finally, a clinical trial involving 30 female participants was conducted, employing the same time-coordinated application scheme.

Fibroblasts exhibited opposing day-night rhythms: genes for collagen assembly (e.g., LOX) peaked during the day, while those involved in synthesis/secretion (e.g., Sec61a2, Mia3, Pde4d, Vps33b) and degradation (e.g., CTSK, MMP1) peaked at night. Time phase-dependent interventions showed baicalin enhanced daytime assembly, while PT-1 boosted nighttime synthesis. In mice, a timed day-night combination therapy increased collagen fiber density. Clinical trial (n = 30) confirmed the efficacy, showing significant improvements in skin luminance (+16.29%), nasolabial fold depth (-36.35%), and firmness (R2: +24.35%).

Collagen metabolism is regulated by circadian rhythms. Chronomodulated baicalin and PT-1 application synergistically optimize collagen metabolism and improve skin quality.