Phytochemical‐Based Modulation of IL‐4Rα for Developing Plant‐Derived Therapeutics Against Eczema: Insights From In Silico Screening, ADMET Profiling and Molecular Dynamics

Abstract

Abstract Eczema, a chronic inflammatory skin disorder, affects a significant portion of the global population, leading to itching, redness, and skin damage. This study investigates the potential of 39 phytochemicals derived from Atractylis cancellata, Helianthemum sessiliflorum, and Euphorbia guyoniana as IL‐4Rα modulators for the development of plant‐derived therapeutics against eczema. Using advanced molecular docking and molecular dynamics simulations, we evaluated the binding affinity, stability, and potential efficacy of these compounds in targeting IL‐4Rα. Our results demonstrate that 10 compounds show strong binding affinity, with values ranging from −12.421 kcal/mol to −8.157 kcal/mol. Among these, Isoolivil and Catechin stood out as particularly promising compounds. Both demonstrated favorable ADMET properties for topical administration, suggesting minimal irritation and optimal skin penetration. In terms of stability, both compounds exhibited RMSD fluctuations below 2 Å during 100 ns molecular dynamics simulations, indicating stable and effective binding to IL‐4Rα. The study also highlights the anti‐inflammatory and immunomodulatory properties of these compounds, suggesting their potential use in topical therapeutic formulations for eczema treatment. These findings provide a foundation for further experimental studies and the development of novel, plant‐derived therapies for inflammatory skin diseases.