Targeting Circadian Rhythm for the Regulation of Skin Collagen Metabolism

  • J Cosmet Dermatol. 2026 Jan;25(1):e70638. doi: 10.1111/jocd.70638.
Cheng Wang  1 ,  Tianlin Song  1 ,  Yurong Zhang  1 ,  Nihong Li  2  3 ,  Ling Xie  2  3 ,  Min Xie  2  3 ,  Xingwu Jiang  4 ,  Guanglei Lü  4 ,  Yun Meng  1 ,  Chaochao Wang  1 ,  Lijun Yue  1 ,  Wei Yang  1 ,  Yang Li  4 ,  Yelin Wu  1 ,  Liang Chen  2  3
Affiliations
  • 1. Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, P. R. China.
  • 2. Scientific Research Laboratory, Shanghai Le-Surely Biotechnology Co. Ltd, Shanghai, P. R. China.
  • 3. SASELOMO Research Institute and Biological Laboratory, Shanghai Chuanmei Industrial Co. Ltd, Shanghai, P. R. China.
  • 4. Zhejiang Key Laboratory of Extreme Environment Functional Materials, Yiwu Research Institute of Fudan University, Yiwu, China.
PMID: 41527525 DOI: 10.1111/jocd.70638
Abstract

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

Aims: 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.

Methods: 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.

Results: 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%).

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

Keywords
baicalin; circadian rhythm; collagen metabolism; palmitoyl tripeptide‐1; skin aging.
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