Clinical Efficacy and Mechanisms of ZiyuShuang , an Anti‐Skin Aging Formula Identified Through Network Medicine Framework Analysis

ABSTRACT Background Skin aging, a key aspect of physiological decline, markedly affects appearance, making strategies to delay it vital for quality of life. Materials and Methods We applied network medicine analysis to screen herbal medicines from the TCMSP database, yielding an anti‐skin aging formula, ZiYuShuang (ZYS). Its efficacy and mechanisms were evaluated using network pharmacology, in vitro assays, and clinical trials. Results Of 155 herbal medicines identified with anti‐skin aging potential from TCMSP, Qi‐reinforcing drugs were most effective. Informed by literature and preliminary data, we developed ZYS. Network pharmacology linked ZYS's effects to Focal Adhesion, Relaxin Signaling, PI3K‐Akt, TNF, and Apoptosis pathways. In vitro, ZYS regulated elastin, collagen (types I, III, IV, VII), and decorin expression. Clinically, ZYS enhanced skin hydration, glossiness, transparency, dermal density, and thickness, while reducing redness, yellowness, firmness, roughness, and wrinkle severity (forehead lines, nasolabial folds, crow's feet, and total facial lines). Conclusion ZYS, derived from network medicine, emerges as a potent adjunct for skin aging interventions.