Mechanism of oligofructans from Ophiopogon japonicus root extract on cutaneous inflammation, barrier function, and microbial defenses in an in vitro atopic dermatitis model

Summary: Abstract Body: Background: Prescription therapies for Atopic Dermatitis(AD) predominantly target the dysregulated inflammatory burden, while over the counter(OTC) products repair the barrier dysfunction and aid the implicated cutaneous dysbiosis. Mechanistic data supporting clinical findings is often lacking for OTC ingredients. To address this gap, oligofructan extract(OFE) from the Ophiopogon japonicus plant, which has shown improvement of clinical symptoms in patients with AD, was investigated in vitro. Methods: Reconstructed epidermis(RE) from normal human keratinocytes and RE with altered barrier function (RE-ABF, treated with sodium lauryl sulfate) were prepared. Experimental RE-ABF samples were exposed to OFE, Poly I:C, TNFα, IL-4/IL-13; select samples were exposed to Staphylococcus aureus. ELISA, flow cytometry, PCR, microscopy, and immunohistochemistry assessed inflammatory byproduct and barrier protein levels. H&E staining, lucifer yellow penetration, and transepithelial resistance assessed barrier integrity/resistance. Mann-Whitney-Wilcoxon and Student’s t test were performed. Results: Systemic 0.04% OFE reduced synthesis of TSLP (-31%) and IL-8 (-20%). Treatment with 0.15% OFE inhibited production of IL-4, IL-13, and IL-31, increased expression of TLR2 (+80%), TLR6 (+69%), HBD2 (+117%), HBD3 (+52%), and RNase7 (+74%), and limited S. aureus adhesion/biofilm formation (-63%). 0.15% OFE application increased claudin-1 (+59%), loricrin (+21%), and filaggrin (+250%) while reducing epidermal permeability (-60%) and improving skin barrier electric resistance (all results reported as change from baseline and at p<0.05). Conclusion: These findings provide mechanistic insights into OFE’s clinical activity. Specifically, OFE treatment reduced keratinocyte-mediated and Th2 inflammation, limited S. aureus adhesion/biofilm formation, and improved skin barrier function, integrity, and resistance. Savanna Vidal¹, Nikita Menta¹, Cleo Whiting¹, Nadège Lachmann², Adam Friedman¹, Elodie Aymard³, Brigitte Closs³ 1. The George Washington University, Washington, DC, United States. 2. Global Sensitive Skincare Faculty, Galderma SA, Lausanne, Switzerland. 3. R&D, Silab, Brive, France. Translational Studies: Preclinical