Chemico-biological interaction unraveled the potential mechanistic pathway of Ixeridium dentatum compounds against atopic dermatitis

This study aims to investigate the potential therapeutic application of Ixeridium dentatum (ID) in treating atopic dermatitis (AD) through network pharmacology, molecular docking, and molecular dynamic simulation. We employed GC-MS techniques and identified 40 bioactive compounds present in the ID and determined their targets by accessing public databases. The convergence of compounds and dermatitis related targets led to the identification of 32 common genes. Among them, IL1B, PTGS2, IL6, IL2, and RELA, were found to be significant targets which were analyzed using Cytoscape network topology. The KEGG pathway evaluation revealed that these targets were significantly enriched in the C-type lectin receptor signaling pathway. The therapeutic efficacy of Stigmasta-5,22-dien-3-ol, Urea, n-Heptyl-, and 3-Epimoretenol was demonstrated in molecular docking assay, as evidenced by their presence in the core compounds of the compound-target network. Furthermore, these compounds exhibited significant kinetic stability and chemical reactivity in DFT quantum analysis when compared to their co-crystallized ligands and reference drug, indicating their potential as key targets for future research. Among the top three docking complexes, namely IL6–3-Epimoretenol, and IL2- Stigmasta-5,22-dien-3-ol, both demonstrated exceptional dynamic characteristics in molecular dynamics simulations at 100 ns. The feasibility of these compounds could be attributed to the prior traditional interrelationship between ID and AD. Overall, this research elucidates the interplay between AD-associated signaling pathways and target receptors with the bioactive ID. The proposal posits the utilization of antecedent compounds as a substitute for the customary pharmaceutical intervention that obstructs the discharge of cytokines, which incite dermal inflammation in the C-type lectin receptor signaling pathway of atopic dermatitis. [Display omitted] •Ixeridium dentatum (ID) is used as remedial for skin inflammation and atopic dermatitis (AD).•GC-MS explored 40 compounds which interplay with IL1B, PTGS2, IL6, IL2, and RELA genes for AD progression.•Those genes enriched in C-type lectin receptor signaling pathway for the regulatory cascades of this AD.•Network pharmacology revealed that Stigmasta-5,22-dien-3-ol, Urea, n-Heptyl-, and 3-Epimoretenol were the key compounds.•Molecular docking and dynamics simulation further corroborated their interactive association significantly.