An Innovative Serum With Retinol, Hydroxypinacolone Retinoate, Peptides, and Silybin Improves Mild Photoaged Facial Skin in Middle‐Aged Chinese Women

ABSTRACT Background Retinoids are effective anti‐aging agents, but their use is often limited by irritation, particularly in Asian skin. Hydroxypinacolone retinoate (HPR), a novel retinoid ester, offers similar benefits with reduced irritation, yet its combined use with retinol remains poorly characterized. Additionally, the integration of peptides and botanical antioxidants like silybin into retinoid‐based regimens lacks mechanistic and clinical evidence. Aims To investigate the molecular mechanisms and clinical efficacy of a novel serum containing retinol, HPR, peptides, and silybin in improving mild photoaged facial skin in Chinese women. Methods Mechanistic effects were investigated using transcriptomic profiling in a keratinocyte–fibroblast co‐culture and protein expression analysis in UV‐exposed ex vivo skin models. Clinical efficacy was assessed in an 8‐week study in middle‐aged Chinese women with mild photoaging. Results Retinol + HPR synergistically activated TGF‐β/Smad signaling and enhanced extracellular matrix gene expression compared with retinol alone. The addition of silybin further promoted collagen and elastin synthesis. Clinically, the serum significantly improved wrinkles, elasticity, hydration, barrier function, and pigmentation with excellent tolerability. Conclusions This multi‐active serum demonstrates a synergistic, well‐tolerated anti‐aging effect. To our knowledge, this work provides an integrated molecular‐to‐clinical evaluation of a retinol‐HPR‐peptide‐silybin combination, supporting its potential as a potent yet gentle anti‐aging option for sensitive skin.