Mechanism of Gu-Ben-Hua-Shi (AESS) Formula Regulating Autophagy Through Hippo-YAP Pathway in Restoring the Skin...

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and immune balance disorders. Currently, drugs for repairing the skin barrier in AD are limited. The gu-ben-hua-shi formula (AESS) has been shown to regulate Th1/Th2/Th17/Treg imbalance with good clinical effect. However, its effects on regulating autophagy, repairing the skin barrier, and interacting with Yes-associated protein (YAP) remain unknown. To elucidate the therapeutic effects of AESS on AD and to investigate its mechanism of restoring skin barrier function through the Hippo-YAP pathway. We conducted a single-arm observational study to evaluate the clinical efficacy of the AESS in patients with AD. Network pharmacology was used to predict the potential therapeutic targets and mechanisms. AD mouse models were established by house dust mite stimulation in Nishiki-nezumi Cinnamon/Nagoya mice, and the effects on autophagy and the skin barrier were measured using western blotting, immunofluorescence, mRFP-GFP-LC3 tandem fluorescence assay, and transmission electron microscopy. The effects of AESS serum on an AD-like inflammatory cell model were detected in HaCaT cells stimulated with interferon-γ (IFN-γ)/tumour necrosis factor-α (TNF-α). Activity of the Hippo-YAP signalling pathway was also investigated after YAP knockdown. AESS improved skin rash and barrier function, reduced eosinophil counts, and increased Th1/Th2 and Treg/Th17 ratios in patients with AD. AESS increased autophagy, improved skin barrier function, and inhibited Hippo-YAP signalling pathway activity. YAP knockdown reduces these therapeutic effects. Besides regulating immune imbalance, AESS increases keratinocyte autophagy levels, thereby restoring skin barrier function in AD through the Hippo-YAP signalling pathway. Trial Registration: The Chinese clinical trial registration website: ITMCTR202500042.